WO2010142060A1

WO2010142060A1 - Lhrh antagonist with long potency and low histamine releasing effect

Info

Publication number: WO2010142060A1
Application number: PCT/CN2009/000648
Authority: WO
Inventors: 刘克良; 周宁; 高永清; 荣嫡; 付慧君; 林凡程; 张文录; 周文霞; 张永祥; 程军平
Original assignee: 中国人民解放军军事医学科学院毒物药物研究所
Priority date: 2009-06-11
Filing date: 2009-06-11
Publication date: 2010-12-16

Abstract

The present invention provides decapeptide derivatives with LHRH receptor antagonizing activity, pituitary gonadotrophin secretion inhibiting effect, and sex gland steroid hormone secretion inhibiting effect, the preparation process thereof, the pharmaceutical composition thereof, the use in the treatment of prostate cancer, endometrial cancer, and reproductive sex hormone dependence related disease, as well as the use in the contraception, etc.

Description

低副作用的 L H拮抗木領域 Low side effects of L H antagonism

本涉及具有 L 休拮抗活性的、具有抑制休分泌性腺激素作用、抑制性腺分泌激素作用的十衍生物其制各方法它們的物組合物及它們在治行*** 、子宮內膜、生殖有夫的性激素依賴相夫疾病、避孕等中的用途。背景木 The present invention relates to a ten-derivative having an action of inhibiting the secretory glandular hormone and inhibiting the action of the secretory gland-secreting hormone, and a composition thereof, and a method for treating the prostate, the endometrium, and the reproductive Sex hormones are used in contraceptive diseases, contraception, and the like. Background

L ( 休生成釋放激素)是由下丘分泌的激素，它的主要作用是促迸休合成休生成 (L )和卵泡刺激素(F ) *** 有和生殖、生有及性激素相夫。 L 由十氨基酸組成，含有。 L 的下所示 L (Hume-producing hormone) is a hormone secreted by the inferior colliculus. Its main function is to promote the synthesis of sputum (L) and follicle stimulating hormone (F). Adolescence has a relationship with reproduction, birth and sex hormones. L consists of ten amino acids and contains . L is shown below

p u p e y y Leu rg o y H₂ L 拮抗 L 作用而抑制 L 的釋放，因此可以用于性激素相夫疾病 *** 等的治行。相比， L 拮抗刑具有速度快、上沖現象、、血清激素水平可等。可以預料， L 拮抗治行前的行化于，更患者接受，比刑具有更大的前景。 Pupeyy Leu rg oy H ₂ L antagonizes L action and inhibits the release of L, so it can be used for the treatment of sex hormones such as prostate. In contrast, L antagonism has a fast speed, an overshoot phenomenon, and a serum hormone level. It can be expected that L antagonism before the treatment of the line, more patient acceptance, has greater prospects than punishment.

目前所的 L 拮抗然已有很，但作力 At present, the L antagonism is already very good, but the effort

，大數仍然存在生物利用度低，休半衰期，釋放高等不足之，限制了 L 拮抗刊在床上的。另外，它矣相似， L 拮抗也很口服收。我們所，目前上市的 L 拮抗都是非口服往。因此，本的目的就是通 L 改造，增或非境的定性未休內作用周期及增生物活性，提高拮抗的生物利用度降低其組副作用，而得到未低甚至可口服的新型 L 拮抗。容 Large numbers still have low bioavailability, half-life, and high release, which limits L antagonism to be published in the bed. In addition, it is similar, and L antagonism is also very oral. Our company, the currently listed L antagonists are non-oral. therefore, The purpose of this study is to transform L, to increase or not the qualitative internal cycle and biological activity, to improve the bioavailability of antagonism and reduce the side effects of the group, and to obtain a new L antagonism that is not low or even oral. Capacity

本明研究現已十衍生物 The present study has now ten derivatives

a pa aa e aa a aa aa o a a pa aa e aa a aa aa o a

或休休或生理毒性，不具有良好的 L 拮抗活性、較長的休作用同以及較低的組釋放副作用，部分化合物甚至具有口服活性。因此 (1)十衍生物或休休或生理毒性可作力物用于*** 、子宮膜、避孕以及其它性激素依賴相夫疾病治行的用途。本方面涉及化合物其 (1 十衍生物或休休或生理毒性，Or rest or physiological toxicity, does not have good L antagonistic activity, longer resting effect, and lower group release side effects, some compounds even have oral activity. Therefore, (1) Ten derivatives or rest or physiological toxicity can be used for the treatment of prostate, uterine membrane, contraception and other sex hormone-dependent diseases. This aspect relates to a compound thereof (a ten derivative or resting or physiological toxicity,

pa aa e aa a aa aa P o a Pa aa e aa a aa aa P o a

其中， among them,

可、 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) 或 ( ) Yes , ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) or ( )

、，、和相互立地可分別，含有或不含有、磷酸、等的取代或未取代的，直或，取代或未取代的，，直或或者，取代或未取代的，直或氧基，取代或未取代的，直或，取代或未取代的，直或，取代或未取代的，，直或氧基或者氧基，取代或未取代的，，直或或者，取代或未取代的，，直或或者，或 , , and , and may or may not contain, substituted or unsubstituted, straight or substituted or unsubstituted, straight or or substituted, or Unsubstituted, straight or oxy, substituted or unsubstituted, straight or substituted or unsubstituted, straight or substituted or unsubstituted, straight or oxy or oxy, substituted or unsubstituted, straight Or alternatively, substituted or unsubstituted, straight or or, or

( ,) ， ( ,) ( ) ， ( ) (例 ( ,) , ( ,) ( ) , ( ) (example

或 ( ，) ，，， ( ，) ( ， Or ( , ) , , , ( ,) ( ,

" "

或 ( ，) ) 或 Or ( ,) ) or

、磷酸、可以是介或 p 立地連接在、，、，和的任何介碳原子上 Phosphoric acid, which may be attached to p or any of the carbon atoms of , , , , and

、 n和 p可分別立地的，例如 1，，， , , n and p can be placed separately, for example 1, , , ,

其中，，中 1 ( 1 ) 立地自、和等的原子的基因未取代的或立地素，硝基，或的取代羊取代或取代或取代的或羊或芳香苯基或者等可未取代的或立地自素硝基，或的取代羊取代或取代的、含有 1 立地自、和等的原子的、、或羊或芳香基因，，等 Wherein, , in the 1 (1) position, and the atom of the unsubstituted gene or the genomic, nitro, or substituted sheep substituted or substituted or substituted or sheep or aromatic phenyl or the like may be unsubstituted or A gene, or a sheep or an aromatic gene, substituted or substituted by a substituted sheep, containing an atom, and or

可， ( ) ) v)或(v) Yes, ( ) ) v) or (v)

其中， among them,

立地的，例， 1，，，，或，，、，和，相互立地可分別、取代或未取代的 Sites, examples, 1, , , , or , , , , , , , , , , , , , , , , , , , ,

" "

，直或，取代或未取代的，，直或或者，取代或未取代的，直或氧基，取代或未取代的，直或，取代或未取代的，直或 , straight or , substituted or unsubstituted, straight or or, substituted or unsubstituted, straight or oxy, substituted or unsubstituted, straight or substituted or unsubstituted, straight or

或 ( ，) ， ( ，) ( ，) ( ，) (例，，或 ( ，) ， Or ( , ) , ( , ) ( , ) ( ,) (example, , or ( ,) ,

( ) ， ( ) , 或 ( ) ) q 立地的，例如 1，，，或 ( ) , ( ) , or ( ) ) q on the ground , for example 1, , , or

B可，或， B can, or ,

，相互立地可分別、取代或未取代的，直或，取代或未取代的，，直或或者 Reciprocal, substituted or unsubstituted, straight or substituted, unsubstituted, straight or

取代或未取代的，直或氧基，取代或未取代的 0 直或取代或未取代的，直或 Substituted or unsubstituted, straight or oxy, substituted or unsubstituted, straight or substituted or unsubstituted, straight or

或 ( ， ( ，) ， ( ，， ( ，) 例，，或 ( ，) ，，， ( ，) ， Or ( , ( , ) , ( , , ( , ) , , , or ( , ) , , , ( ,) ,

( ，) 或 ( ( , ) or (

" ，) )，或， q 立地的整數，例， 1，，，，或 " , ) ), or , q the integer of the place, for example, 1, , , , or

其中，化，中 1 ( 1 ) 立地自、和等的原子的基因未取代的或立地自素，硝基，或的取代羊取代或取代或取代的、、或羊或芳香基因，如苯基或者等可未取代的或立地自鹵素硝基，或的取代羊取代或取代的、含有 1 立地自、和等的原子的、或羊或芳香，，，等Where, chemistry, medium 1 ( 1 a gene that is unsubstituted or substituted by a gene, or a substituted or substituted or substituted sheep, or a sheep or an aromatic gene, such as a phenyl or an unsubstituted or standing Substituted or substituted by a halogen nitro group, or a substituted sheep, containing an atom, or a sheep or aroma, , , etc.

aa 可 Phe或 D P Aa can be Phe or D P

aa , aa 和 aa 各立地可 L或型的 he )Phe( ) Phe( ph( c op phe> ph p ph g o p n n Ly y n o n t 或者 ph中的任何 Aa , aa and aa each may be L or type he )Phe( ) Phe( ph( c op phe> ph p ph g o p n n Ly y n o n t or any of ph

或者 or

aa, aa 或 aa 可相互立地可力以下 ( )或 (1 ) 的 Aa, aa or aa can stand side by side with the following ( ) or (1)

其中， among them,

( ) - ( ) > ( ) ( P( > P( ) )P( ) ) " ( ) - ( ) > ( ) ( P( > P( ) )P( ) ) "

( ( ) ( ) 或 ( ( ) ( ) or

- ( ) ( ) - ( ) ( )

( ) ( ) 或 ( ) ( ) or

可立地的整數，例如， 1，，，，或相 0) " " 互立地可分別 ( ) 、An integer that can be placed, for example, 1, , , , or Phase 0) "" can stand separately ( ),

( ) ，其中和，分別，取代或未取代的直或，取代或未取代的，，直或或者，取代或未取代的直或氧基，取代或未取代的G ，直或或 ( ，) ， ( ), wherein, and, respectively, substituted or unsubstituted straight or substituted or unsubstituted, straight or substituted, unsubstituted or unsubstituted straight or oxy, substituted or unsubstituted G, straight or or (,) ,

( ，) ， ( ，) ， ( ，) 例，或 ( , ) , ( , ) , ( , ) , , or

( ) ， ( ， 1 ( ) 或 ( ) , ( , 1 ( ) or

( ，) )，或， n 立地的整數，例， 1，，，或 ( ,) ), or , n the integer of the place, for example, 1, , , or

其中，，中 1 ( 1 ) 立地自、和等的原子的基因未取代的或立地自鹵素，硝基，或的取代羊取代或取代或取代的、、或羊或林芳香基因苯基或者等可未取代的或立地素，硝基，或的取代羊取代或取代的、含有 1 立地自和等的原子的、、或羊或芳香基因如，，等 Wherein, , in the 1 (1) site, and the atomic genes of the atom are unsubstituted or substituted from halogen, nitro, or substituted sheep substituted or substituted or substituted, or sheep or forest aromatic gene phenyl or the like An unsubstituted or substituted lysine, a nitro group, or a substituted or substituted, equimolar or aromatic atom, or a sheep or aromatic gene such as,

aa 可 Leu, c 或 c 在本 (1)十衍生物或休休或生理毒性中，的是， c Aa may be Leu, c or c in this (1) derivative or rest or physiological toxicity, c

Enan h 、Lau 、 P y 、 Buty y 、 o noy 、 gony 、 n > P pe dy o pho ny 、或 t. Enan h , Lau , P y , Buty y , o noy , gony , n > P pe dy o pho ny , or t.

在本 (1)十衍生物或休休或生理毒性，的是， B ，。 In this (1) ten derivative or resting or physiological toxicity, is B,.

在本 (1)十衍生物或休休或生理毒性中，的是, aa he( ) Phe( ) Phe( ) ph( c) op phe ph p P o Uph g n u p h ( ) Ph ( ). In this (1) ten derivative or rest or physiological toxicity Among them, aa he( ) Phe( ) Phe( ) ph( c) op phe ph p P o Uph gnuph ( ) Ph ( ).

在本 (1)十衍生物或休休或生理毒性 L中，化的是, a a he( ) he( ) he( ) ph( c) o p op he ph ph D g n D n u p Phe In the (1) derivatives or rest or physiological toxicity L, a a he( ) he( ) he( ) ph( c) o p op he ph ph D g n D n u p Phe

he( ) ph(Lau y ) p (Pa y ) ph uty y ) , ph co noy ) D p ( e a gony ) ph( Et) ph( n ) ph( pe dy ) ph( o pho n ) ph( )或 ph( Et) 在本 (1)十衍生物或休休或生理，中的是, a g Ly n n或 n He( ) ph(Lau y ) p (Pa y ) ph uty y ) , ph co noy ) D p ( ea gony ) ph( Et ) ph( n ) ph( pe dy ) ph( o pho n ) ph( ) Or ph( Et) in this (1) ten derivative or rest or physiology, is ag Ly nn or n

在本 (1)十衍生物或休休或生理毒性中，的是 aa Leu, c 或 c 。本的介方面涉及各本 (1)十衍生物的方法。 ( )d 衍生物的各固相合成方法方法以 B In the (1) derivatives or rest or physiological toxicity, aa Leu, c or c. This section refers to the method of each (1) ten derivative. Solid phase synthesis method for ( )d derivatives

休， oc 策略，到未。 Hugh, oc strategy, to no.

(1)十衍生物的各方法 1 中方案 1所示。 (1) Ten derivatives of each method 1 shown in Scheme 1.

方法包括以下步驟將十位的保的氨基酸原料以 / B 或 B / E 合 B The method includes the following steps: the quaternary amino acid raw material is / B or B / E

反完全 /二氧 Bo 1 E 中和下介氨基酸原料按此順序依次將十氨基酸都到上將最終所得到的 F裂解( F 苯甲 g L . L 裂解溫度 C 裂解同 )得到，其中平均含量裂解完成，水，水 ( 19 L) ，，化。 The anti-complete/dioxane Bo 1 E neutralizing and lowering amino acid starting materials are obtained in this order, in which the ten amino acids are sequentially obtained by the final F cracking (F benzoyl g L. L pyrolysis temperature C is cleaved). The average content of the cracking is completed, water, water (19 L), and chemistry.

化可以用中化 ( 化 F a h 反相 1 otage公休 2 / . 醋酸水)，化得到大于的。 1所示方案 1表示本 ( 1 ) 十衍生物的各方法。本的介方面涉及特和B 接到上 (1)十衍生物或休休或生理毒性上的方法。 It can be neutralized (chemical F a h reversed 1 otage public 2 / . acetic acid water), and the larger is obtained. Scheme 1 shown in Figure 1 represents the methods of this (1) ten derivative. This aspect refers to the method by which B and B are attached to (1) derivatives or rest or physiological toxicity.

本的介方面涉及含至少上 (1)十衍生物或合物。本的介方面涉及本 (1)十衍生物或休休或生理毒性在各于預防或治行性激素相夫疾病 ( 性激素相夫癌症， *** 、子宮膜、乳腺 )或避孕的物中的用途。 This aspect relates to a derivative or compound containing at least (1) ten. This mediation relates to the use of this (1) derivative or rest or physiological toxicity in the prevention or treatment of sex hormones (sex hormones, prostate, mucous membrane, mammary gland) or contraception.

本的介方面涉及本 (1)十衍生物或休休或生理毒性在各于拮抗、拮抗 L 休、抑制休分泌性腺激素( 和/或F )和/或抑制性腺分泌矣激素( 口***、激素和/或 )的物中的用途。 This mediation relates to the present (1) derivatives or rest or physiological toxicity in each of the antagonistic, antagonistic L-suppression, inhibition of the secretory glandular hormone (and / or F) and / or inhibition of the gonadotropin-suppressing hormone (oral estrogen , the use of hormones and / or).

本的介方面涉及本 (1)十衍生物或休休或生理毒性在各于降低、、反等的物中的用途。本的介方面涉及預防或治行性激素相夫疾病 ( 性激素相夫癌症， *** 、子宮膜、乳腺 )或避孕的方法，方法包括給予患者或避孕者有效量的 (1 十衍生物或休休或生理毒性。 The present invention relates to the use of the present (1) derivatives or rest or physiological toxicity in each of reduced, reversed, etc. This aspect relates to a method for preventing or treating a sex hormone related disease (sex hormones, prostate, uterine membrane, breast) or contraception, and the method includes administering an effective amount to a patient or a contraceptive (1 derivative or rest or Physiological toxicity.

本的介方面涉及拮抗、拮抗 L 休、抑制休分泌性腺激素(例和/或F )和/或抑制性腺分泌矣激素( 口***、激素和/或 )的方法，方法給予需要者有效量的 (1)十衍生物或休休或生理毒性。 The present invention relates to a method for antagonizing, antagonizing L-happiness, inhibiting secretory glandular hormones (such as and/or F), and/or inhibiting gonadotropin-suppressing hormones (oral estrogen, hormones and/or), and administering an effective amount to a subject in need thereof. (1) Ten derivatives or rest or physiological toxicity.

本的介方面涉及降低釋放、、反等的方法，方法包括給予需要者有效量的 (1)十衍生物或休休或生理毒性。本的介方面涉及 ( ) ( )及所示化合物或衍生物, Boc he( 、 Boc he( ) Boc he( ) Boc he( t ) Boc he( ) Boc p u e do he This aspect relates to methods for reducing release, reversal, etc., including administering an effective amount of (1) ten derivatives or rest or physiological toxicity. This aspect refers to ( ) ( ) and the compound or derivative shown, Boc he( , Boc he( ) Boc he( ) Boc he( t ) Boc he( ) Boc p u e do he

E > L Boc Ly (F oc) L Boc n(F oc) L Boc Ly (Bz F oc) oc p(F oc) > 、或衍生物。 E > L Boc Ly (F oc) L Boc n (F oc) L Boc Ly (Bz F oc) oc p(F oc) > , or a derivative.

本的介方面涉及 ( )、 (1 1)及所示化合物或衍生物的各，例 Boc h ( ) Boc he( ) Boc he( ) Boc he( 8u ) Boc he( ) Boc p u e do he EL Boc Ly (F oc) L oc n(F oc) 、 L Boc Ly (Bz ,F oc) Boc p(F oc) t 或衍生物的各。 The mediation relates to ( ), (1 1) and each of the compounds or derivatives shown, for example Boc h ( ) Boc he( ) Boc he( ) Boc he( 8u ) Boc he( ) Boc pue do he EL Boc Ly (F oc) L oc n(F oc) , L Boc Ly (Bz , F oc) Boc p(F oc) t Or each of the derivatives.

本的介方面涉及 ( ) )及所示化合物或衍生物, Boc he( ) Boc he( ) Boc he( ) oc he( 、 Boc he( ) Boc p u e do he This aspect refers to ( ) ) and the compound or derivative shown, Boc he( ) Boc he( ) Boc he( ) oc he( , Boc he( ) Boc p u e do he

> E L Boc Ly (F oc) L oc n(F oc) > E L Boc Ly (F oc) L oc n(F oc)

L oc Ly ( z ,F oc) oc p(F oc) u 、或衍生物等在降低、、反方面的用途。本所用木 " (1)十衍生物休休"是指相的或 L 休。本的化方案，本 (1)十衍生物或休休或生理毒性自下面的十或休休或生理毒性的The use of L oc Ly ( z , F oc) oc p(F oc) u , or a derivative thereof in reducing, and inversely. The wood used in this article is "(1) Ten Derivatives Rest" means phase or L. The present scheme, this (1) derivative or rest or physiological toxicity from the following ten or rest or physiological toxicity

) c a pa a e g a Leu g a ) c a pa a e g a Leu g a

( ) a pa he e g a Leu g o a ( ) a pa he e g a Leu g o a

( ) aP pa Pa e g Pa Leu g o a ( ) aP pa Pa e g Pa Leu g o a

( ) a pa he e n Pa Leu g o a ( ) a pa he e n Pa Leu g o a

( ) a pa a e n a Leu g o a ( ) a pa a e n a Leu g o a

( ) c a pa he e n Pa Leu g o a -- -( ) ca pa he en Pa Leu goa -- -

(7)Ac D Na Gl-n D-Pa-6(7)Ac D Na Gl-n D-Pa-6

l Le-u' Ar-g P - 0 --rD-Cp-a D-Pa-l Se-r' l Le-u' Ar-g P - 0 --rD-Cp-a D-Pa-l Se-r'

ro D-A-la1 N-H Ro D-A-la1 N-H

(8)NH CO D Nal1 D Cpa D Phe Ser Gln D Pal Leu Arg Pro D Ala10 (8) NH CO D Nal1 D Cpa D Phe Ser Gln D Pal Leu Arg Pro D Ala10

NH NH

(9)NH-CO-D--N-al1-D--C-pa-D--Pal--Ser--G-ln-D--Pal--Leu--Arg - -P-ro-D--Ala1-NH (9) NH-CO-D--N-al1-D--C-pa-D--Pal--Ser--G-ln-D--Pal--Leu--Arg--P-ro- D--Ala1-NH

(10)D-Na1'-D-Cpa-D-P 9 he-Ser-Asn-D-Pa 6 (10) D-Na1'-D-Cpa-D-P 9 he-Ser-Asn-D-Pa 6

1-Leu-Arg-Pro-D-Alal-NH 1-Leu-Arg-Pro-D-Alal-NH

(11)D-Na-rD-Cp-a D-Pa-l Se-r' As-n D-Pa-l Le-u Ar-g Pr-o D A-la-l NH- (11) D-Na-rD-Cp-a D-Pa-l Se-r' As-n D-Pa-l Le-u Ar-g Pr-o D A-la-l NH-

(12)Ac D Na(12)Ac D Na

1-0 - r-D-Cpa-D-Phe-Ser-Asn-D-Pal-Leu-Arg- Pro-D-Ala-NH 1-0 - r-D-Cpa-D-Phe-Ser-Asn-D-Pal-Leu-Arg- Pro-D-Ala-NH

(13)Ac D NaT D Cpa D Pa1 Ser Asn D Pa 6 (13)Ac D NaT D Cpa D Pa1 Ser Asn D Pa 6

1 Leu Arg 9 1 Leu Arg 9

Pro D AlaI NHPro D AlaI NH

(14)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Asn--D-- 6 (14) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Asn--D-- 6

Pal--Leu--Ar g--Pro--D--Ala10--NH Pal--Leu--Ar g--Pro--D--Ala10--NH

(15)N-H CO-D-Nal'-D-Cpa -D Pal-Ser--Asn -D Pal-Leu-Ar 9 (15) N-H CO-D-Nal'-D-Cpa -D Pal-Ser--Asn -D Pal-Leu-Ar 9

- g-Pro D A- g-Pro D A

?- la10 ?- la10

NH NH

(16)D-Nal1-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Arg-Pro -D-Ala'-NH (16) D-Nal1-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Arg-Pro-D-Ala'-NH

(17)D-Na-l1 D-Cp-a D-Pa-l Se-r Mp-h D-Pa-l Le-u Ar-g Pr-o D A-la-l NH- (17) D-Na-l1 D-Cp-a D-Pa-l Se-r Mp-h D-Pa-l Le-u Ar-g Pr-o D A-la-l NH-

(18)Ac D NarD Cpa D Phe Ser Mph D Pal Leu Arg 9 (18)Ac D NarD Cpa D Phe Ser Mph D Pal Leu Arg 9

Pro D Ala10Pro D Ala10

NH NH

(19)Ac-D-Nar-D-Cpa-D-Pal-Ser-Mph-D- 6 (19)Ac-D-Nar-D-Cpa-D-Pal-Ser-Mph-D- 6

Pal-Leu-Arg- Pro-D-Ala10-NH - -- -Pal-Leu-Arg- Pro-D-Ala10-NH - -- -

(20)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Ar g-Pro-D-Ala10-NH (20) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Ar g-Pro-D-Ala10-NH

(21)NH CO D NaT D Cpa D Pa1 Ser Mph D Pa1 Leu Ar g Pro D Ala10 (21) NH CO D NaT D Cpa D Pa1 Ser Mph D Pa1 Leu Ar g Pro D Ala10

NH NH

s (22)Ac--D--Nal'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg8-- Pro--D--Ala10--NH s (22)Ac--D--Nal'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg8-- Pro--D-- Ala10--NH

(23)Ac-D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg- Pro-D-Ala10-NH (23)Ac-D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg- Pro-D-Ala10-NH

(24)Ac-D Nal1 D Cpa D-Phe-Ser-Uph D Mo (24)Ac-D Nal1 D Cpa D-Phe-Ser-Uph D Mo

9 0 - -- - -p-Leu-Arg-0 Pro-D Al-a1-NH - 9 0 - -- - -p-Leu-Arg-0 Pro-D Al-a1-NH -

(25)Ac-D-Nal1-D-Cpa-D-Phe-Ser'-Phe(NAM)-D-Mop-Leu- Arg-Pro-D-Ala10-NH (25)Ac-D-Nal1-D-Cpa-D-Phe-Ser'-Phe(NAM)-D-Mop-Leu- Arg-Pro-D-Ala10-NH

(26)Ac D Nal1 D Cpa D Phe Ser Phe(NNM) D Mop Leu Arg8 Pro9 D AlaI0 (26)Ac D Nal1 D Cpa D Phe Ser Phe(NNM) D Mop Leu Arg8 Pro9 D AlaI0

NH NH

s (27)Ac--D--Nar--D--Cpa--D--Phe--Ser'--Phe(NOM)---D-Mop--Leu-- Arg--Pro---D-Ala-10-NH s (27)Ac--D--Nar--D--Cpa--D--Phe--Ser'--Phe(NOM)---D-Mop--Leu-- Arg--Pro-- -D-Ala-10-NH

(28)Ac D Nal' D Cpa-D-Phe-Ser-Aph(Ac) -D M-o 6 p -Leu -A - 9 -- -- rg Pro -D-Ala1 -NH (28)Ac D Nal' D Cpa-D-Phe-Ser-Aph(Ac) -D M-o 6 p -Leu -A - 9 -- -- rg Pro -D-Ala1 -NH

(29)A-c D N-al-1 D C-pa-D P-he S-er A-ph-(DMe)- D M-op L-eu -Ar-g Pro-D Ala10 (29) A-c D N-al-1 D C-pa-D P-he S-er A-ph-(DMe)- D M-op L-eu -Ar-g Pro-D Ala10

NH NH

(30)D-Nal1-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg-Pro -D-Alal-NH (30) D-Nal1-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg-Pro-D-Alal-NH

(31)D NarD Cpa D Phe Ser Aph D Mop Leu A 9 rg Pro D A 1 (31)D NarD Cpa D Phe Ser Aph D Mop Leu A 9 rg Pro D A 1

U NH U NH

(32)D-Nar-D-Cpa-D-Phe-Ser-Uph-D-Mop-Leu-Arg-Pro -D-Alal-NH - -- -(32) D-Nar-D-Cpa-D-Phe-Ser-Uph-D-Mop-Leu-Arg-Pro -D-Alal-NH - -- -

(33)D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mo 6(33) D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mo 6

p-Leu-Arg -Pro-D-Ala1-NH p-Leu-Arg -Pro-D-Ala1-NH

(34)D NarD Cpa D Phe Ser Phe(NOM) D Mo 6 (34)D NarD Cpa D Phe Ser Phe(NOM) D Mo 6

p Leu Arg Pro D Ala1 NH p Leu Arg Pro D Ala1 NH

s (35)D--Nar--D--Cpa--D--Phe--Ser--Aph(Ac)--D-M-op--Leu--Arg --Pro--D--Ala10--NH s (35)D--Nar--D--Cpa--D--Phe--Ser--Aph(Ac)--DM-op--Leu--Arg --Pro--D--Ala10- -NH

(36)D Nar--D Cpa--D Phe--Ser -Aph(D-Me) -D-Mop-Leu-Arg -Pro -D-Ala10 (36)D Nar--D Cpa--D Phe--Ser -Aph(D-Me) -D-Mop-Leu-Arg -Pro -D-Ala10

-NH -NH

(37)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Phe-D-Mop-Leu-Ar0 g-Pro-D-Ala10-NH (37) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Phe-D-Mop-Leu-Ar0 g-Pro-D-Ala10-NH

(38)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Aph-D-Mop-Leu-Ar g-Pro-D-Ala10-NH (38) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Aph-D-Mop-Leu-Ar g-Pro-D-Ala10-NH

(39)NH CO D Nal1 D Cpa D Phe Ser' Uph D Mo 6 (39) NH CO D Nal1 D Cpa D Phe Ser' Uph D Mo 6

p Leu Ar g Pro D Ala10 p Leu Ar g Pro D Ala10

NH NH

s (40)NH CO--D--Nal'--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Le u--Arg--P 9s (40)NH CO--D--Nal'--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Le u--Arg--P 9

ro--D--Ala10--NH ro--D--Ala10--NH

(41)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D 6 (41) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D 6

-Mop-Le u-Arg-Pro-D-Ala1-NH -Mop-Le u-Arg-Pro-D-Ala1-NH

(42)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-Le u-Arg-Pro--D Ala-1 NH (42) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-Le u-Arg-Pro--D Ala-1 NH

(43)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac) -D M-o 6 (43) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac) -D M-o 6

p -Leu A-rg -Pro -D A-la10-NH p -Leu A-rg -Pro -D A-la10-NH

(44)NH CO D NarD Cpa D Phe Ser Aph(DMe) D Mo 6 p Le u Arg Pro D Ala10 (44) NH CO D NarD Cpa D Phe Ser Aph (DMe) D Mo 6 p Le u Arg Pro D Ala10

NH NH

(45)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg -Pro-D-Ala10-NH - -- -(45) NTA-D-Nal'-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg-Pro-D-Ala10-NH - -- -

(46)NTA D NarD Cpa D Phe Ser Aph D Mop6(46) NTA D NarD Cpa D Phe Ser Aph D Mop6

Leu Arg Pro9 Leu Arg Pro9

D Ala10 D Ala10

NH NH

(47)NTA (47)NTA

9 -D 9 -D

0 -Nal1 0 -Nal1

-D-Cpa-D-Phe 6 -D-Cpa-D-Phe 6

-Ser-Uph D Mo-p-Leu-Arg -Pro-D Al-a1-NH - (48)NTA--D--Nal'--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Leu- -Arg--Pro--D--Ala10 -Ser-Uph D Mo-p-Leu-Arg -Pro-D Al-a1-NH - (48)NTA--D--Nal'--D--Cpa--D--Phe--Ser-- Phe(NAM)--D--Mop--Leu--Arg--Pro--D--Ala10

--NH --NH

(49)NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)--D Mop-Leu A - rg-Pro--D Ala-1 NH (49) NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)--D Mop-Leu A - rg-Pro--D Ala-1 NH

(50)NTA-D-Nal' D Cpa 6 (50)NTA-D-Nal' D Cpa 6

D Phe Ser Phe(NOM) D Phe Ser Phe (NOM)

0 -- -- - - -D-Mop-Leu -Arg-Pro-D-Ala1-NH 0 -- -- - - -D-Mop-Leu -Arg-Pro-D-Ala1-NH

(51)NTA D NarD Cpa D Phe Ser Aph(Ac) D Mop Leu Arg Pro9 D Ala1 NH (51) NTA D NarD Cpa D Phe Ser Aph(Ac) D Mop Leu Arg Pro9 D Ala1 NH

( 6 52)NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph(-DM-e) D-Mop-Leu -Arg-P-ro9 D-Ala!0 ( 6 52)NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph(-DM-e) D-Mop-Leu -Arg-P-ro9 D-Ala!0

NH NH

(53)NDN--D--Nal'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg- -Pro--D--Ala10--NH (53)NDN--D--Nal'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg--Pro--D--Ala10 --NH

(54)NDN-D (54)NDN-D

0 -Nar-D-Cpa-D-Phe-Ser-Aph D Mo-p-Leu-Arg -Pro-D Al-a1 0 -Nar-D-Cpa-D-Phe-Ser-Aph D Mo-p-Leu-Arg -Pro-D Al-a1

-NH - -NH -

(55)NDN-D-Nar-D-Cpa-D-Phe-Ser-Uph D Mo-p6(55)NDN-D-Nar-D-Cpa-D-Phe-Ser-Uph D Mo-p6

-Leu-Arg -Pro-D Al-a10 -Leu-Arg -Pro-D Al-a10

-NH - -NH -

(56)NDN D NarD Cpa D Phe Ser Phe(NAM) D Mo 6(56)NDN D NarD Cpa D Phe Ser Phe(NAM) D Mo 6

p Leu Arg Pro D Ala1 NH p Leu Arg Pro D Ala1 NH

(57)NDN D Nal' D Cpa D Phe Ser Phe(NNM) D Mop Leu Arg Pro D Ala10 (57)NDN D Nal' D Cpa D Phe Ser Phe(NNM) D Mop Leu Arg Pro D Ala10

NH NH

(58)NDN-D-Na1'-D-Cpa-D-Phe-Ser-Phe(NOM)-D-Mop-Leu -Arg- 9 (58)NDN-D-Na1'-D-Cpa-D-Phe-Ser-Phe(NOM)-D-Mop-Leu-Arg- 9

Pro-D-Ala10-NH - -- -Pro-D-Ala10-NH - -- -

(59)NDN-D-Nar-D-Cpa-D-Phe-Ser'-Aph(Ac) -op -Leu - o -D-A a10 -D M (59)NDN-D-Nar-D-Cpa-D-Phe-Ser'-Aph(Ac) -op -Leu - o -D-A a10 -D M

Arg -Pr l -NH Arg -Pr l -NH

(60)NDN D Na1' D Cpa' D Phe'Ser' Aph(DMe) D Mo 6 (60)NDN D Na1' D Cpa' D Phe'Ser' Aph(DMe) D Mo 6

p Leu Arg Pro D Ala10 p Leu Arg Pro D Ala10

NH NH

(61)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe--Leu--Arg-- Pro--D--Ala1--NH (61)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe--Leu--Arg-- Pro--D--Ala1- -NH

(62)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg- Pro-D-Ala1-NH (62)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg- Pro-D-Ala1-NH

(63)Ac-D-NalI-D-Cpa-D-Phe-Ser-Mop-D-Up 6 (63)Ac-D-NalI-D-Cpa-D-Phe-Ser-Mop-D-Up 6

h Leu-Arg-Pro-D Al-a10-NH - h Leu-Arg-Pro-D Al-a10-NH -

(64)Ac-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu- Arg-Pro-D-Ala1-NH (64)Ac-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu- Arg-Pro-D-Ala1-NH

(65)Ac D Nal1 D Cpa D Phe Ser Mop D Phe(NNM) Leu Arg Pro D Ala10 (65)Ac D Nal1 D Cpa D Phe Ser Mop D Phe(NNM) Leu Arg Pro D Ala10

NH NH

(66)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)-6-Leu-- Arg--Pro---D-AlaI-0-NH (66)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)-6-Leu-- Arg--Pro--- D-AlaI-0-NH

(67)Ac-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(Ac) -Leu -A rg -Pro -D-Ala1 -NH (67)Ac-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(Ac) -Leu -A rg -Pro -D-Ala1 -NH

(68)A-c D N-al-' D C-pa-D P-he S-er M-op-D A-ph(DM-e)6 (68) A-c D N-al-' D C-pa-D P-he S-er M-op-D A-ph(DM-e)6

L-euA -r-g Pro-9 L-euA -r-g Pro-9

D Ala10 D Ala10

NH NH

(69)D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe6-Le 9 u-Arg-Pro -D-Alal-NH (69) D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe6-Le 9 u-Arg-Pro -D-Alal-NH

(70)D Nal1 D Cpa D Phe Ser Mop D Aph Leu Arg Pro D AlaI0 (70)D Nal1 D Cpa D Phe Ser Mop D Aph Leu Arg Pro D AlaI0

NH NH

(71)D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph-Leu-Arg-Pro -D-Alal-NH - -- -(71) D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph-Leu-Arg-Pro-D-Alal-NH - -- -

(72)D Nal1 D Cpa D Phe Ser Mop D Phe(NAM) Leu Arg Pro D Ala10(72)D Nal1 D Cpa D Phe Ser Mop D Phe(NAM) Leu Arg Pro D Ala10

NH NH

(73)D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6 (73) D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6

-Leu-Arg -Pro-D-Ala10 -Leu-Arg -Pro-D-Ala10

-NH -NH

(74)D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)--Leu--Arg --Pro--D--Ala10 (74) D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)--Leu--Arg --Pro--D--Ala10

--NH --NH

(75)D Nar--D Cpa--D Phe--Ser M-op -D Aph-(A-c) L-eu A-rg P-ro D-A-la10 (75)D Nar--D Cpa--D Phe--Ser M-op -D Aph-(A-c) L-eu A-rg P-ro D-A-la10

N-H N-H

(76)D Nar--D Cpa--D Phe--Ser -Mop -D Aph-(D-Me) -Leu-Arg -Pro -D-AlaI0 (76)D Nar--D Cpa--D Phe--Ser -Mop -D Aph-(D-Me) -Leu-Arg -Pro -D-AlaI0

-NH -NH

(77)NH C0 D Na C 6 (77)NH C0 D Na C 6

pa D Phe r g Pro D Ala10 rD Ser' Mop D Phe Leu A Pa D Phe r g Pro D Ala10 rD Ser' Mop D Phe Leu A

NH NH

(78)NH C0-D-Nar 6 (78) NH C0-D-Nar 6

-D-Cpa-D-Phe-Ser-Mop-D-Aph Leu-Ar g-Pro-D Al-a1 C - (79)NH O-NH --D -D-Cpa-D-Phe-Ser-Mop-D-Aph Leu-Ar g-Pro-D Al-a1 C - (79)NH O-NH --D

aI --Nal1 aI --Nal1

--D--Cpa--D--Phe--Ser'--Mop--D--Uph6-Leu--Ar g--Pro--D-Al- --D--Cpa--D--Phe--Ser'--Mop--D--Uph6-Leu--Ar g--Pro--D-Al-

(80)NH C--NH - 0-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Le u-Arg-Pro-D-Ala10(80) NH C--NH - 0-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Le u-Arg-Pro-D-Ala10

-NH -NH

(81)NH CO-D-Nar-D Cpa D Phe Ser Mop D Phe(NNM) Leu A -- - - -- - - rg-Pro--D Ala1 (81) NH CO-D-Nar-D Cpa D Phe Ser Mop D Phe(NNM) Leu A -- - - -- - - rg-Pro--D Ala1

-NH- -NH-

(82)NH C0 D Nal' D Cpa' D Phe'Ser' Mop' D Phe(N0M) Le u Arg Pro9(82)NH C0 D Nal' D Cpa' D Phe'Ser' Mop' D Phe(N0M) Le u Arg Pro9

D Ala1 NH D Ala1 NH

(83)NH C0 D Na1' D Cpa D Phe Ser Mop D Aph(Ac)6 (83)NH C0 D Na1' D Cpa D Phe Ser Mop D Aph(Ac)6

Leu Arg Pro D Ala10 Leu Arg Pro D Ala10

NH NH

(84)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(DMe)6-Le u-Arg-Pro-D-Ala10-NH - -(84) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(DMe)6-Le u-Arg-Pro-D-Ala10-NH - -

(85- )NTA- D NarD Cpa D Phe Ser -Mop-D-Phe-Leu-Arg Pro9(85- )NTA- D NarD Cpa D Phe Ser -Mop-D-Phe-Leu-Arg Pro9

D Ala10 D Ala10

NH NH

(86)NTA-D (86)NTA-D

0 -Na1'-D-Cpa-D-Phe-Ser' -Mop-D-Aph-Leu-Arg -Pro-D Al-a1 0 -Na1'-D-Cpa-D-Phe-Ser' -Mop-D-Aph-Leu-Arg -Pro-D Al-a1

- (87)NTA-NH - (87)NTA-NH

--D--Na1'--D--Cpa--D--Phe--Ser' -Mop-D-Uph-Leu-Arg8 - -Pro--D-Al-a10 --D--Na1'--D--Cpa--D--Phe--Ser' -Mop-D-Uph-Leu-Arg8 - -Pro--D-Al-a10

--NH --NH

(88)NTA - -D-Na1'-D-Cpa-D-Phe-Ser' -Mop-D-Phe(NAM)-Leu -Arg-Pro-D-Ala1 (88)NTA - -D-Na1'-D-Cpa-D-Phe-Ser' -Mop-D-Phe(NAM)-Leu -Arg-Pro-D-Ala1

-NH -NH

(89)NTA-D-Nar-D-Cpa-D-Phe-Ser' -Mop-D-Phe(NNM)-Leu A 0 (89)NTA-D-Nar-D-Cpa-D-Phe-Ser' -Mop-D-Phe(NNM)-Leu A 0

rg-Pro--D Ala1 rg-Pro--D Ala1

-NH -NH

(90)NTA D NarD Cpa D Phe Ser' -Mop-D-Phe(NOM)-Leu Arg Pro D Ala1 NH (90) NTA D NarD Cpa D Phe Ser' -Mop-D-Phe(NOM)-Leu Arg Pro D Ala1 NH

(91)NTA-D-Nar-D-Cpa-D-Phe-Ser -Mop-D-Aph(Ac)-Leu- - Arg -Pr-o D A-la10 (91)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)-Leu- - Arg -Pr-o D A-la10

NH NH

(92)NTA -Mop-D-Aph(DMe)-Leu - 9 (92) NTA -Mop-D-Aph(DMe)-Leu - 9

-Arg--P-ro-D--D-Arg--P-ro-D--D

---Nar--D--Cpa--D--Phe--Ser ---Nar--D--Cpa--D--Phe--Ser

-Ala10-NH -Ala10-NH

(93)NDN-D-Nar-D-Cpa-D-Phe-Ser - 。 (93) NDN-D-Nar-D-Cpa-D-Phe-Ser - .

Mop一D一Phe-Leu'-Arg -Pro-D-Ala10 Mop-D-Phe-Leu'-Arg-Pro-D-Ala10

-NH -NH

(94)NDN-D-Nal! (94)NDN-D-Nal!

-D-Cpa-D-Phe-Ser' -Mop-D-Aph-Leu-Arg -Pro-D Al-a1 -D-Cpa-D-Phe-Ser' -Mop-D-Aph-Leu-Arg -Pro-D Al-a1

-NH - -NH -

(95)NDN D NarD Cpa D Phe Ser -Mop-D-Uph-rLe_(95)NDN D NarD Cpa D Phe Ser -Mop-D-Uph-rLe_

u.'-Al _ rg Pro D Ala10 u.'-Al _ rg Pro D Ala10

NH NH

(96)NDN D Nal' D Cpa D Phe Ser -Mop-D-Phe(NAM)-Leu Arg Pro9 D Ala10 (96)NDN D Nal' D Cpa D Phe Ser -Mop-D-Phe(NAM)-Leu Arg Pro9 D Ala10

NH NH

(97)NDN-D-Nal!-D-Cpa-D-Phe-Ser -Mop-D-Phe(NNM)-Leu -Arg-Pro-D-Ala10-NH - - -- -(97)NDN-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Leu-Arg-Pro-D-Ala10-NH - - -- -

(98)NDN D Na Mop(98)NDN D Na Mop

9 -- r-D-Cpa-D-Phe-Ser- -D-Phe(NOM)-Leu- Arg-Pro--D Ala-10 9 -- r-D-Cpa-D-Phe-Ser- -D-Phe(NOM)-Leu- Arg-Pro--D Ala-10

NH NH

(99)NDN D Nal' D Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala10 (99)NDN D Nal' D Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala10

NH NH

(100)ND-N--D-Nal-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph-(DMe)--Le - u-Ar-g--Pro--D-Ala10-NH (100) ND-N--D-Nal-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph-(DMe)--Le - u- Ar-g--Pro--D-Ala10-NH

(101)Ac-D-Nar-D-Cpa-D-Phe-Ser-Leu-D-Mop-Leu-Arg- 9 (101)Ac-D-Nar-D-Cpa-D-Phe-Ser-Leu-D-Mop-Leu-Arg- 9

Pro-D-Ala10-NH Pro-D-Ala10-NH

(102)Ac-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mop-Leu-Arg -Pro-D-Ala10-NH (102)Ac-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mop-Leu-Arg-Pro-D-Ala10-NH

(103)Ac-D-Nal'-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-Arg -Pro-D-Ala1-NH (103)Ac-D-Nal'-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-Arg-Pro-D-Ala1-NH

(104)Ac D Nal1 D Cpa D Phe Ser Glu D Mop Leu Arg Pro9 D Ala10 (104)Ac D Nal1 D Cpa D Phe Ser Glu D Mop Leu Arg Pro9 D Ala10

NH NH

(105)Ac--D--Nal1--D--Cpa--D--Phe--Ser'--Gln--D--Mop--Leu--Arg - -Pro--D--Ala10--NH (105)Ac--D--Nal1--D--Cpa--D--Phe--Ser'--Gln--D--Mop--Leu--Arg--Pro--D--Ala10 --NH

(106)A-c D N-al-! D C-pa-D P-he S-er' A-rg-D M-op L-eu A-rg P-ro-D A-la10 (106) A-c D N-al-! D C-pa-D P-he S-er' A-rg-D M-op L-eu A-rg P-ro-D A-la10

NH NH

(107)D-Na1!-D-Cpa-D-Phe-Ser-Leu-D-Mop-Leu-A 8 rg-Pro-D-Ala10-NH (107) D-Na1!-D-Cpa-D-Phe-Ser-Leu-D-Mop-Leu-A 8 rg-Pro-D-Ala10-NH

(108)D-Nar-D-Cpa D Phe-Ser-Tyr-D-Mop-Leu-Arg-Pr o-D-Ala10 -- -NH (108) D-Nar-D-Cpa D Phe-Ser-Tyr-D-Mop-Leu-Arg-Pr o-D-Ala10 ---NH

(109)D NarD Cpa D Phe Ser Lys D Mop Leu Arg Pr o D Ala10 (109)D NarD Cpa D Phe Ser Lys D Mop Leu Arg Pr o D Ala10

NH NH

(110)D-Na1'-D-Cpa'-D-Phe'-Ser'-GIu-D-Mop6-Leu-Arg-Pr o-D-Ala10-NH -- -(110)D-Na1'-D-Cpa'-D-Phe'-Ser'-GIu-D-Mop6-Leu-Arg-Pr oD-Ala10-NH -- -

(111)D Nal1 6(111)D Nal1 6

-D-Cpa-D-Phe-Ser'-Gln-D-Mop-Leu-Arg-Pr o-D-Ala1 - -NH -D-Cpa-D-Phe-Ser'-Gln-D-Mop-Leu-Arg-Pr o-D-Ala1 - -NH

(112)D Nal1 D Cpa D Phe Ser Arg D Mop Leu Arg Pr o D Ala10 (112)D Nal1 D Cpa D Phe Ser Arg D Mop Leu Arg Pr o D Ala10

NH NH

(113)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Leu--D--Mop6 (113)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Leu--D--Mop6

--Leu--A rg--Pro--D--Ala10--NH --Leu--A rg--Pro--D--Ala10--NH

(114)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mo 6 (114) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mo 6

p-Leu-A rg-Pro-D-Ala10-NH p-Leu-A rg-Pro-D-Ala10-NH

(115)NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-A rg- 9 (115) NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-A rg- 9

Pro-D-Ala10-NH Pro-D-Ala10-NH

(116)NH CO-D-Nar-D-Cpa-D-Phe-Ser-GIu-D-Mop-Leu-A rg-P 9 (116) NH CO-D-Nar-D-Cpa-D-Phe-Ser-GIu-D-Mop-Leu-A rg-P 9

ro-D-Ala1-NH ro-D-Ala1-NH

(117)NH CO D NarD Cpa D Phe Ser Gln D Mop Leu A rg Pro D Ala10 (117) NH CO D NarD Cpa D Phe Ser Gln D Mop Leu A rg Pro D Ala10

NH NH

(118)N-H CO--D--Nal1--D--Cpa--D-Phe--Ser-Arg--D--Mop-6-Leu--A rg--Pro-9--D-Ala-1-NH (118) NH CO--D--Nal1--D--Cpa--D-Phe--Ser-Arg--D--Mop-6-Leu--A rg--Pro-9--D- Ala-1-NH

(119)D N-a1-' D C-pa-' D P-he-' Ser-' Phe-(NNM) D Mo-p-Leu-Ar g -Pro -D Ala-10 (119)D N-a1-' D C-pa-' D P-he-' Ser-' Phe-(NNM) D Mo-p-Leu-Ar g -Pro -D Ala-10

-NH - -NH -

( 6 120)NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-Leu-' Arg-Pro--D Ala-10( 6 120)NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-Leu-' Arg-Pro--D Ala-10

NH NH

(121)NTA-D-Nar-D-Cpa-D-Phe-Ser'-Phe(-CA-M) D Mop -Le u -Arg -Pro D--Ala10-NH (121) NTA-D-Nar-D-Cpa-D-Phe-Ser'-Phe(-CA-M) D Mop -Le u -Arg -Pro D--Ala10-NH

(122)NTA D NarD Cpa D Phe Ser Mop D Phe(COOH) L eu Arg Pro D Ala10 (122) NTA D NarD Cpa D Phe Ser Mop D Phe(COOH) L eu Arg Pro D Ala10

NH NH

(123)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)6-Le u-Arg-Pro-D-Ala10-NH - - --(123)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)6-Le u-Arg-Pro-D-Ala10-NH - - --

(124)NDN D Nal1- D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-L eu-Arg-P 9-- - ro--D Ala-10(124)NDN D Nal1- D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-L eu-Arg-P 9-- - ro--D Ala-10

NH NH

(125)NDN D NarD Cpa D Phe Ser' Phe(CAM) D Mop Le u Arg Pro D Ala1 NH (125)NDN D NarD Cpa D Phe Ser' Phe(CAM) D Mop Le u Arg Pro D Ala1 NH

(126)NDN--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Phe(COOH)6 (126)NDN--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Phe(COOH)6

--L eu--Arg--Pro---D-Ala-1-NH --L eu--Arg--Pro---D-Ala-1-NH

( 6 127)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10-NH ( 6 127)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10-NH

(128)CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg-Pro-D-Ala1-NH (128) CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg-Pro-D-Ala1-NH

(129)CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Le u-Arg-Pro-D-Ala10-NH (129) CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Le u-Arg-Pro-D-Ala10-NH

(130)CAM D Na1' D Cpa' D Phe' Ser' Mop' D Phe(NOM)6 (130)CAM D Na1' D Cpa' D Phe' Ser' Mop' D Phe(NOM)6

Le u Arg Pro D Ala1 NH Le u Arg Pro D Ala1 NH

(131)CAM--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Phe(CAM)--Le u'--Arg--Pro--D--Ala10--NH (131)CAM--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Phe(CAM)--Le u'--Arg --Pro--D--Ala10--NH

(132)CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(COOH)-L eu-Arg-Pro--D Ala-10 (132) CAM-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(COOH)-L eu-Arg-Pro--D Ala-10

NH NH

(133)CEC D Na1' D Cpa (NAM) (133)CEC D Na1' D Cpa (NAM)

9 -- -- '-D-Phe'-Ser'-Mop'-D-Phe -Leu-Arg-Pro-D-Ala10-NH 9 -- -- '-D-Phe'-Ser'-Mop'-D-Phe -Leu-Arg-Pro-D-Ala10-NH

(134)CEC-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Le u-Arg-Pro-D-Ala1-NH (134) CEC-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Le u-Arg-Pro-D-Ala1-NH

(135)CEC D NarD Cpa D Phe Ser Mop D Phe(NOM) Le u Arg Pro D Ala10 (135) CEC D NarD Cpa D Phe Ser Mop D Phe (NOM) Le u Arg Pro D Ala10

NH NH

(136)CEC-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10-NH - - -- -(136) CEC-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10-NH - - -- -

(137)CEC-D-Nal'-D-Cpa-D-Phe-Ser-Mop D Ph-e(C-OOH)-L eu-Arg-Pro--D Ala-1 NH (137) CEC-D-Nal'-D-Cpa-D-Phe-Ser-Mop D Ph-e(C-OOH)-L eu-Arg-Pro--D Ala-1 NH

(138)CAM D Na1' D Cpa D Phe Ser Phe(NAM) D Mo 6 p Le u Arg Pro D Ala10 (138)CAM D Na1' D Cpa D Phe Ser Phe(NAM) D Mo 6 p Le u Arg Pro D Ala10

NH NH

s (139)CAM--D--Na1'--D--Cpa--D--Phe--Ser--Phe(NNM)--D--Mop--Le u--Arg--Pro--D--Ala1--NH s (139)CAM--D--Na1'--D--Cpa--D--Phe--Ser--Phe(NNM)--D--Mop--Le u--Arg--Pro- -D--Ala1--NH

(140)CAM (140) CAM

Pro9 -D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)-D-M 6 op-Le u-Arg- -D-Ala10-NH Pro9 -D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)-D-M 6 op-Le u-Arg- -D-Ala10-NH

(141)CAM-D-Nal'-D-Cpa'-D-Phe'-Se 6 r'-Phe(CAM) -D M-op -Le0 u -Arg -Pro -D-Ala10-NH (141) CAM-D-Nal'-D-Cpa'-D-Phe'-Se 6 r'-Phe(CAM) -D M-op -Le0 u -Arg -Pro -D-Ala10-NH

(142)CAM-D-Nal'-D-Cpa'-D-Phe'-Ser'-Phe(COOH)--D Mop-L eu-Arg-Pro--D Ala-10 (142) CAM-D-Nal'-D-Cpa'-D-Phe'-Ser'-Phe(COOH)--D Mop-L eu-Arg-Pro--D Ala-10

NH NH

(143)CEC D Na1' D Cpa D Phe Ser Phe(NAM) D Mop Le u Arg8 (143)CEC D Na1' D Cpa D Phe Ser Phe(NAM) D Mop Le u Arg8

Pro9 D AlaI NH Pro9 D AlaI NH

(144)CEC--D--Nar--D--Cpa--D--Phe--Ser'--Phe(NNM)--D--Mop--Le u--Arg--Pro--D--Ala10--NH (144) CEC--D--Nar--D--Cpa--D--Phe--Ser'--Phe(NNM)--D--Mop--Le u--Arg--Pro-- D--Ala10--NH

(145)CEC-D-Na1' D Cpa-D-Phe-Ser-Phe(NOM) 6 (145) CEC-D-Na1' D Cpa-D-Phe-Ser-Phe(NOM) 6

-D-Mop-Le u-Arg-Pro9-D-Ala10-- -NH -D-Mop-Le u-Arg-Pro9-D-Ala10-- -NH

(146)CEC-D-Nar-D-Cpa-D-Phe-Ser (146) CEC-D-Nar-D-Cpa-D-Phe-Ser

10 -Phe(CAM) -D M-op -Le u -Arg -Pro -D-Ala -NH 10 -Phe(CAM) -D M-op -Le u -Arg -Pro -D-Ala -NH

(147)CEC D-N-al' D Cpa D Phe S-e 6 r P-he(C-OO-H) D-Mop eu-Arg-P- 0 -- -- -L ro D-Ala1 NH (147) CEC D-N-al' D Cpa D Phe S-e 6 r P-he(C-OO-H) D-Mop eu-Arg-P- 0 -- -- -L ro D-Ala1 NH

(148)NH CO D Nal' D Cpa D Phe Ser Aph D Ap 6 h Leu A rg Pro D Ala10 (148) NH CO D Nal' D Cpa D Phe Ser Aph D Ap 6 h Leu A rg Pro D Ala10

NH NH

(149)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Aph-Leu-A rg-Pro9-D-Ala10-NH - -- -(149) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Aph-Leu-A rg-Pro9-D-Ala10-NH - -- -

(150)NH CO-D Na(150) NH CO-D Na

0 - r-D-Cpa-D-Phe-Ser'-Uph-D-Aph-Leu-A rg-Pro-D-Ala1-NH 0 - r-D-Cpa-D-Phe-Ser'-Uph-D-Aph-Leu-A rg-Pro-D-Ala1-NH

(151)NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph'-D-Uph'-Leu'-A rg Pro9 D Ala10 (151) NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph'-D-Uph'-Leu'-A rg Pro9 D Ala10

NH NH

(152)NH CO D NarD Cpa D Phe-Ser-Gln-D-Uph-Leu-A rg--Pro--D--Ala1-0 - -- -- --NH (152) NH CO D NarD Cpa D Phe-Ser-Gln-D-Uph-Leu-A rg--Pro--D--Ala1-0 - -- -- --NH

(153)NH CO D Nar-D-Cpa-D-Phe-Ser-Uph D U-ph-Leu-A rg 9 -- -Pro-D A-la-10 (153) NH CO D Nar-D-Cpa-D-Phe-Ser-Uph D U-ph-Leu-A rg 9 -- -Pro-D A-la-10

NH- NH-

(154)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Uph Leu-Arg-Pro-D Al-a1-NH (154) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Uph Leu-Arg-Pro-D Al-a1-NH

(155)NH CO-D NaI1 - D Cpa-D-Phe-Ser-Aph(-Ac-) D Aph(-Ac )-Leu-Arg-P-9- -- ro D-Ala10 (155) NH CO-D NaI1 - D Cpa-D-Phe-Ser-Aph(-Ac-) D Aph(-Ac )-Leu-Arg-P-9- -- ro D-Ala10

NH NH

(156)NH CO D Nal1 D Cpa D Phe Ser' Gln D Aph(Ac) Le u Arg Pro D Ala1 NH (156) NH CO D Nal1 D Cpa D Phe Ser' Gln D Aph(Ac) Le u Arg Pro D Ala1 NH

(157)NH CO--D--Nar--D--Cpa--D--Phe--Ser'--Uph--D--Aph(-Ac)--Le u--Arg--Pr-o9-D-A-la10-NH (157) NH CO--D--Nar--D--Cpa--D--Phe--Ser'--Uph--D--Aph(-Ac)--Le u--Arg--Pr -o9-DA-la10-NH

(158)NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph Leu-C it-Pro-D A-la-1 NH- (158) NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph Leu-C it-Pro-D A-la-1 NH-

(159)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(-Ac) -Leu C-it P-ro9-D Al-a10(159) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(-Ac) -Leu C-it P-ro9-D Al-a10

NH NH

(160)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-I Iys-Pro9 (160) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-I Iys-Pro9

-D-Ala10-NH -D-Ala10-NH

(161)NH CO D NarD Cpa D Phe Ser Mop D Ap 6 (161) NH CO D NarD Cpa D Phe Ser Mop D Ap 6

h Leu I orn Pro D Ala10 h Leu I orn Pro D Ala10

NH NH

(162)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-A rg-Pro9-D-Ala10-NH (163)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Pro-D-Mop-Leu-A rg--Pro--D--Ala1--NH (162) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-A rg-Pro9-D-Ala10-NH (163) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Pro-D-Mop-Leu-A rg--Pro--D--Ala1--NH

(164)NH CO--D--Nal!--D--Cpa--D--Phe--Ser--Mop--D--Aph--Leu--G (164) NH CO--D--Nal!--D--Cpa--D--Phe--Ser--Mop--D--Aph--Leu--G

In Pro D Ala1 NHIn Pro D Ala1 NH

(165)NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu L ys(Bzl)-Pro-D-Ala1-NH (165) NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu L ys (Bzl)-Pro-D-Ala1-NH

(166)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph-Leu-A sp-Pro-D-Ala1-NH (166) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph-Leu-A sp-Pro-D-Ala1-NH

(167)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Asn-Leu-A rg-Pro9-D-Ala10-NH (167) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Asn-Leu-A rg-Pro9-D-Ala10-NH

(168)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Glu--Leu--A rg--Pro9--D--Ala10--NH (168) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Glu--Leu--A rg--Pro9--D-- Ala10--NH

(169)NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu G Iu Pro D Ala10 (169)NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu G Iu Pro D Ala10

NH NH

(170)NH CO--D--Nal'--D--Cpa--D--Phe--Ser--Mop--D--Aph6-Leu--A sn--Pro--D-A-la-10-NH- (170) NH CO--D--Nal'--D--Cpa--D--Phe--Ser--Mop--D--Aph6-Leu--A sn--Pro--DA-la -10-NH-

(171)NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Amp(-Ac) -Le u A-rg -Pr-o9(171) NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Amp(-Ac) -Le u A-rg -Pr-o9

D A-laI0 D A-laI0

NH NH

(172)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-A 6 (172) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-A 6

mp-Leu-A rg -Pro9 mp-Leu-A rg -Pro9

-D-Ala10 -D-Ala10

N-H N-H

(173)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Mop Leu-I Lys-Pro-D Al-a1-NH - (173) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Mop Leu-I Lys-Pro-D Al-a1-NH -

(174)NH CO D NarD Cpa D Phe Ser Mop D Phe(CAM) L eu Ilys Pro D Ala10(174) NH CO D NarD Cpa D Phe Ser Mop D Phe (CAM) L eu Ilys Pro D Ala10

NH NH

(175)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Amp(Ac)-Le u-Glu-Pro-D-Ala10-NH - -- -(175) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Amp(Ac)-Le u-Glu-Pro-D-Ala10-NH - -- -

(176)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop D M 6(176) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop D M 6

-op-Leu-G Iu P-ro D-Ala-10-NH - -op-Leu-G Iu P-ro D-Ala-10-NH -

(177)NH CO D NarD Cpa D Phe Ser Aph(Ac) D Mop (A cc) A 9(177) NH CO D NarD Cpa D Phe Ser Aph(Ac) D Mop (A cc) A 9

rg Pro D Ala10 Rg Pro D Ala10

NH NH

(178)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Aph(-Ac-)-D-Mop--(A cc)'--Arg--Pro--D--Ala10--NH (178) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Aph(-Ac-)-D-Mop--(A cc)'--Arg-- Pro--D--Ala10--NH

(179)NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(Ac)-(A cc)-Arg-Pro9-D-Ala10-NH (179) NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(Ac)-(A cc)-Arg-Pro9-D-Ala10-NH

(180)NH C-O-D Na-r-D Cp-a-D Ph-e Se-r Mo-p-D Ap-h(Ac)- (Ac-c) -Ar-g Pro-D Ala10 (180) NH C-O-D Na-r-D Cp-a-D Ph-e Se-r Mo-p-D Ap-h(Ac)- (Ac-c) -Ar-g Pro-D Ala10

NH NH

(181)NTA-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Pro6-Leu-Arg -Pro9-D-Ala10-NH (181) NTA-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Pro6-Leu-Arg-Pro9-D-Ala10-NH

(182)NTA D NarD Cpa D Phe Ser Gln D Mop Leu Arg Pro D Ala10 (182) NTA D NarD Cpa D Phe Ser Gln D Mop Leu Arg Pro D Ala10

NH NH

(183)NTA--D--NalI--D--Cpa--D--Phe--Ser--Gln-D-A-ph-(Ac)--Leu -Ar-g-Pr-o-D--Al-a1-NH- (183) NTA--D--NalI--D--Cpa--D--Phe--Ser--Gln-DA-ph-(Ac)--Leu-Ar-g-Pr-oD--Al -a1-NH-

(184)NTA (184) NTA

c) Arg8 -D-Na1'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Mop-(Ac - -Pro9-D-Ala10-NH c) Arg8 -D-Na1'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Mop-(Ac - -Pro9-D-Ala10-NH

(185)NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph(-Ac-) D Mo 6 (185) NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph(-Ac-) D Mo 6

p cc) ro D A 0 p cc) ro D A 0

la1 -(A -Arg8-P -- -NH La1 -(A -Arg8-P -- -NH

(186)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)-(Ac C)-Arg-Pro-D-Ala10-NH (186) NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)-(Ac C)-Arg-Pro-D-Ala10-NH

(187)NTA D NarD Cpa D Phe Ser Mop D Aph(Ac) (Ac c) Arg Pro D Ala10 (187) NTA D NarD Cpa D Phe Ser Mop D Aph(Ac) (Ac c) Arg Pro D Ala10

NH NH

(188)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop- 6 (188) NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop- 6

D-Asn-Leu-Arg -Pro-D-Ala10-NH - -- -D-Asn-Leu-Arg -Pro-D-Ala10-NH - -- -

(189)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Glu-Leu-Arg -Pro-D-Ala1-NH (189) NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Glu-Leu-Arg-Pro-D-Ala1-NH

(190)NTA D Nal' D Cpa D Phe Ser Aph D Mop Leu Arg Pro9 (190) NTA D Nal' D Cpa D Phe Ser Aph D Mop Leu Arg Pro9

D Ala10 D Ala10

NH NH

(191)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(Enanth y1-)-Le-u-Ar-g-Pr-o--D-Al-a10-NH (191) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(Enanth y1-)-Le-u-Ar-g-Pr -o--D-Al-a10-NH

(192)NH CO-D-Nar-D Cpa-D-Phe-Ser'-Mop-D-Aph(Lauryl )6 (192) NH CO-D-Nar-D Cpa-D-Phe-Ser'-Mop-D-Aph(Lauryl)6

L-eu A-rg P-ro9 L-eu A-rg P-ro9

D-A-la10- NH- D-A-la10- NH-

(193)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Palmityl)-Leu-Arg-Pro--D Ala-10(193) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Palmityl)-Leu-Arg-Pro--D Ala-10

NH NH

(194)NH CO-D-Nal1-D-Cpa D Phe Ser Mop D Aph(Butyry 1) Le-u Ar-g Pr-9 (194) NH CO-D-Nal1-D-Cpa D Phe Ser Mop D Aph (Butyry 1) Le-u Ar-g Pr-9

o D-Al NH- o D-Al NH-

(195)NH CO D 1-a10 -- - - -- Nal D Cpa D Phe Ser Mop D Aph(Nicoti noyl) Leu Arg P 9(195) NH CO D 1-a10 -- - - -- Nal D Cpa D Phe Ser Mop D Aph (Nicoti noyl) Leu Arg P 9

ro D Ala10 Ro D Ala10

NH NH

(196)NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Aph(Pe-larg - onyl)--Leu--Arg---Pro-D--Ala10-NH (196) NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Aph(Pe-larg-onyl)--Leu--Arg-- -Pro-D--Ala10-NH

(197)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Uph(Di-E-t) Le-u Ar-g Pr-o9 (197) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Uph(Di-E-t) Le-u Ar-g Pr-o9

D-Al-a10 D-Al-a10

NH- NH-

(198)NH CO-D-Nal1(198) NH CO-D-Nal1

-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di n Pr) -Leu-Arg-Pro9 -D-Cpa-D-Phe-Ser-Mop-D-Uph(Di n Pr) -Leu-Arg-Pro9

-D Al-a10 -D Al-a10

-NH - -NH -

(199)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Piperi dyl C-O) L-eu A-rg P-ro D-A-la10(199) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Piperi dyl C-O) L-eu A-rg P-ro D-A-la10

N-H N-H

(200)NH CO D NarD Cpa D Phe Ser Mop D Aph(Morpho 1iny1 CO) Leu Arg Pro D Ala10 (200) NH CO D NarD Cpa D Phe Ser Mop D Aph (Morpho 1iny1 CO) Leu Arg Pro D Ala10

NH NH

(201)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-i-P r)-Leu-Arg-Pro-D-Ala10-NH (201) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-i-P r)-Leu-Arg-Pro-D-Ala10-NH

? - - - -- -? - - - -- -

(202)NH CO D N-ar-D Cpa-D P-he-Ser-Mop-D U-ph-(Di Et) -Leu-A - -- 0 - rg Pro D Ala1-NH (202) NH CO D N-ar-D Cpa-D P-he-Ser-Mop-D U-ph-(Di Et) -Leu-A - -- 0 - rg Pro D Ala1-NH

(203)Enanthyl D NarD Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala1 NH (203)Enanthyl D NarD Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala1 NH

(204)Lauryl-D--Nal1-D--C-pa-D--P-he-S -M-op-D--A-ph(Ac)- L-eu-A-rg- 9 (204) Lauryl-D--Nal1-D--C-pa-D--P-he-S-M-op-D--A-ph(Ac)- L-eu-A-rg- 9

P-ro-D--A-la1- -er P-ro-D--A-la1- -er

0-N-H 0-N-H

(205)Palmity-l-D Nar--D Cpa--D Phe-Ser-Mop--D Aph(Ac)-Leu-Arg-Pro-D-Ala1-NH (205) Palmity-l-D Nar--D Cpa--D Phe-Ser-Mop--D Aph(Ac)-Leu-Arg-Pro-D-Ala1-NH

(206)Butyryl D-Na-l! D-Cp-a D-Ph-e Se-r Mo-p D-Ap-h(Ac)6 Le-u Ar-g Pr-o D-Al-a10 (206) Butyryl D-Na-l! D-Cp-a D-Ph-e Se-r Mo-p D-Ap-h(Ac)6 Le-u Ar-g Pr-o D-Al-a10

NH- NH-

(207)Nicotinoyl-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(A c)6-Leu-Arg-Pro-D-Ala10(207) Nicotinoyl-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(A c)6-Leu-Arg-Pro-D-Ala10

-NH -NH

(208)Pelargonyl D Nal! D Cpa D Phe Ser Mop D Aph(A c) Leu Arg 9 (208) Pelargonyl D Nal! D Cpa D Phe Ser Mop D Aph(A c) Leu Arg 9

Pro D A 0 Pro D A 0

la1 NH La1 NH

(209)Di--E-t-N-CO-D--N-ar-D--C-pa-D--P-he-S-er-M-op-D--A-ph(Ac )- 9 (209)Di--E-t-N-CO-D--N-ar-D--C-pa-D--P-he-S-er-M-op-D--A-ph(Ac )- 9

L-eu-A-rg-P-ro-D--A-la10-N-H L-eu-A-rg-P-ro-D--A-la10-N-H

(210)Di n Pr N-CO-D-Nar-D-Cpa -D-Phe -Ser M-op -D-Aph( Ac) -Leu -Arg -Pro -D-Ala10 (210) Di n Pr N-CO-D-Nar-D-Cpa -D-Phe -Ser M-op -D-Aph( Ac) -Leu -Arg -Pro -D-Ala10

-NH -NH

(211)Piperidyl C-O D-N-al1 D-C-pa D-P-he S-er M-op D-A-ph (Ac) L-eu A-rg P-ro D-A-la10 (211) Piperidyl C-O D-N-al1 D-C-pa D-P-he S-er M-op D-A-ph (Ac) L-eu A-rg P-ro D-A-la10

N-H N-H

(212)Mo-rp-hol-inyl-C-O D N-al-! D C-pa-D P-he S-er M-op-D A ph(A-c) L-eu A-rg P-ro-D A-la10 (212) Mo-rp-hol-inyl-CO D N-al-! D C-pa-D P-he S-er M-op-D A ph(Ac) L-eu A-rg P-ro- D A-la10

NH NH

(213)Di i Pr NCO D Nal1 D Cpa D Phe Ser Mop D Aph( Ac)6 Leu Arg Pro D Ala10 (213) Di i Pr NCO D Nal1 D Cpa D Phe Ser Mop D Aph( Ac)6 Leu Arg Pro D Ala10

NH NH

(214)Di-Et-NCO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac )6-Leu-Arg-Pro-D-Ala10-NH - - -- -(214) Di-Et-NCO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)6-Leu-Arg-Pro-D-Ala10-NH - - -- -

(215)Ben-zo-y1 D-Na-1! D-Cp-a D-Phe-Ser'-Mo-p D Aph(-Ac) -L eu -Arg -Pr-o D A-la1 NH (215) Ben-zo-y1 D-Na-1! D-Cp-a D-Phe-Ser'-Mo-p D Aph(-Ac) -L eu -Arg -Pr-o D A-la1 NH

(216)CHF D NarD Cpa D Phe Ser Mop D Aph(Ac)6 (216)CHF D NarD Cpa D Phe Ser Mop D Aph(Ac)6

Leu Arg Pro D AlaI NH Leu Arg Pro D AlaI NH

(217)MOB-A--D-Na1-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph(Ac)--Leu- -Arg-8-Pro-9--D-Ala-10-NH (217) MOB-A--D-Na1-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph(Ac)--Leu--Arg- 8-Pro-9--D-Ala-10-NH

(218)CPF D-N-a1' D-C-pa'D-P-he'S-er' M-op' D-A-ph(Ac)-L-eu Arg-Pro a0 (218) CPF D-N-a1' D-C-pa'D-P-he'S-er' M-op' D-A-ph(Ac)-L-eu Arg-Pro a0

-D Al-1 N-H- - -D Al-1 N-H- -

(219)NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di n But -yl) -Leu -Arg -Pr-o D A-la10(219) NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di n But -yl) -Leu -Arg -Pr-o D A-la10

NH NH

(220)NH-CO-D Nal-1 D-Cp-a D-Ph-e Se-r-Mop-D Up-h(Pro 6 (220) NH-CO-D Nal-1 D-Cp-a D-Ph-e Se-r-Mop-D Up-h (Pro 6

-py-l) Leu -Arg -Pro -D Ala-10-NH - -py-l) Leu -Arg -Pro -D Ala-10-NH -

(221)Di n Butyl NCO D Nal! D Cpa D Phe Ser Mop D Ap h(Ac) Leu Arg Pro9(221) Di n Butyl NCO D Nal! D Cpa D Phe Ser Mop D Ap h(Ac) Leu Arg Pro9

D Ala1 NH D Ala1 NH

(222)Bu-ty-ryl-D--N-ar-D--C-pa-D--Phe--Ser--M-op-D-Aph(Butyr y1-)-Le-u-Ar-g8-Pr-o--D-Al-a10-NH (222)Bu-ty-ryl-D--N-ar-D--C-pa-D--Phe--Ser--M-op-D-Aph(Butyr y1-)-Le-u-Ar -g8-Pr-o--D-Al-a10-NH

(223)Ac-D-Nal1-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Pelargony-l ) -Leu -Arg -Pr-o D A-la10 (223)Ac-D-Nal1-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Pelargony-l) -Leu -Arg -Pr-o D A-la10

NH NH

(224)Ac D-Na-l1 D-Cp-a D-Ph-e Se-r Mo-p D-Ap-h(Butyr-yl) Leu-Arg- 9 (224)Ac D-Na-l1 D-Cp-a D-Ph-e Se-r Mo-p D-Ap-h(Butyr-yl) Leu-Arg- 9

Pro-D Al-a1-0 Pro-D Al-a1-0

NH - NH -

(225)NHCO D Nal1 D Cpa D Phe Ser'Mop D Uph(di Penty 1) Leu Arg Pro D Ala10(225)NHCO D Nal1 D Cpa D Phe Ser'Mop D Uph(di Penty 1) Leu Arg Pro D Ala10

NH NH

$LVLikltL,&£L*ft&(I)-hJIk fA$LVLikltL, & £L*ft&(I)-hJIk fA

i tb (23),*(24*A i tb (23),*(24*A

), (25*), (26*),*i.a*'|i|tiitlJ (32), (38), (39), (41), (62), (63), (64), (65), (66), (67), (70), ( 1), ), ( ), ( ), ( ), ), ( 1), ( ) ( ), ( ) ( ), ( ), ( ) ( ), ( ), (1 ), (1 ), (1 ), (1 ) (11 ) (11 ), (11 ), (1 ) (1 ), (1 ) (1 1), (1 ), (1 ), 1 ), (1 1), 1 ), 1 )和(1 . 休方式 ), (25*), (26*), *ia*'|i|tiitlJ (32), (38), (39), (41), (62), (63), (64), (65 ), (66), (67), (70), (1), ), ( ), ( ), ( ), ), ( 1), ( ) ( ), ( ) ( ), ( ), ( ) ( ), ( ), (1 ), (1 ), (1), (1) (11) (11), (11), (1) (1), (1) (1 1), (1), (1), 1), (1 1), 1 ), 1) and (1. Hugh way

在本明中使用的具有下面的 Used in the present invention with the following

c c

c 氨基 c amino

a a

p p

g g

ph 氨基 Ph amino

ph c) Ph c)

ph( e) ( , 二甲 ) 氨基 Ph( e) ( , dimethyl ) amino group

ph(Enanthy ) 氨基 Ph(Enanthy ) amino

ph Lau y ) 月桂 Ph Lau y ) Laurel

ph( a ty ) Ph( a ty )

ph(Bu y y ) Ph(Bu y y )

ph( co noy ) Ph( co noy )

ph( e a gony ) Ph( e a gony )

ph( Et) ( 二乙 ) Ph( Et) ( 二乙 )

ph( n P ) ( ) Ph( n P ) ( )

ph( n p opy ) ( , ) Ph( n p opy ) ( , )

ph( pe dy ) ( ) Aph(Morpho nyl-CO)- 4-(嗎琳甲銑腰基)苯丙氨酸 ph(Di--Pr)- 4-(N,N-二弄丙基脈基)苯丙氨酸 Uph(Di-Et)- 4-(N,N-二乙基脈基)苯丙氨酸 Ph( pe dy ) ( ) Aph(Morpho nyl-CO)- 4-(Molin-milled waist-based) phenylalanine ph(Di--Pr)- 4-(N,N-dipropylpropyl)phenylalanine Uph( Di-Et)- 4-(N,N-diethylcarbyl)phenylalanine

Enanthyl- 庚醜基Enanthyl- 庚丑

Lauryl- 月桂銑 Lauryl- Laurel Milling

Pal ityl- 棕櫚醜 Pal ityl- palm ugly

Butyryl- T銑基 Butyryl-T milling base

Nicotinoyl-炯醜基 Nicotinoyl-炯丑基

PelaIgonyl- 壬銑基PelaIgonyl- boring and milling base

Di-Et- 二乙基 Di-Et-diethyl

Di-n-PI- 二正丙基 Di-n-PI-di-n-propyl

Piperidyl - 派唳基 Piperidyl - 派基基

MoIpholinyl- 嗎琳基 MoIpholinyl-

Di-i-Pr 二弄丙基Di-i-Pr dipropyl

CHF- 杯己基甲銑基 CHF- cup hexyl milling

MOBA- 吋甲氧基苯乙銑基 MOBA- 吋 methoxy phenylethyl milling

CPF- 杯丙基甲銑基 CPF-cup propyl milling base

Asn- 天冬醜肢 Asn- Asparagus

Asp- 天冬氨酸Asp-aspartate

B c- 叔丁氧碳基 B c-tert-butoxy carbon

BOP- 苯井三哇-1-氧-三(二甲氨基)磷六氟磷酸 CAMBOP- benzene well three wow-1-oxy-tris(dimethylamino)phosphonium hexafluorophosphate CAM

J 浚甲基 J 浚 methyl

CEC- 梭乙銑基 CEC- shuttle

Cpa- 4-氯苯丙氨酸Cpa- 4-chlorophenylalanine

CPC- 梭丙銑基 CPC- Shuttle Milling

DCC- 二杯己基碳二亞腰 D EA e 二弄丙基乙腰 DCC- two cups of hexyl carbon dioxide waist D EA e 2 propyl propyl waist

G n- 谷氨銑腰 G n- glutamine milling

G u- 谷氨酸 G u- glutamic acid

HOBt P l-楚基苯井三哇HOBt P l-楚基苯井三哇

i-Pr P 弄丙基 i-Pr P propyl

Leu p 亮氨酸 Leu p leucine

Lys- 賴氨酸 Lys-lysine

Phe(COOH)- 梭基苯丙氨酸 Phe(COOH)- shuttle phenylalanine

Ph (CAM)- 梭甲基苯丙氨酸Ph (CAM)-choline methylphenylalanine

ILys ，弄丙基賴氨酸ILys , propyl lysine

Orn P 弄丙基冉氨酸 Orn P propyl valine

MBHA ，苯基氨甲基村脂 MBHA, phenylaminomethyl glutamate

Mob- B-胡椒基丙氨酸 Mob- B-piperonyl alanine

Mop p 嗎琳甲基苯丙氨酸Mop p morphine methyl phenylalanine

Mph- 胡椒基丙氨酸 Mph-piperonyl alanine

Na - 茶丙氨酸 Na - tea alanine

NTA N,N-二叛乙基氨基乙魷基 NTA N,N-di-alkatoethylaminoethyl

NTA - N,N-(二辛氧碳基甲基)氨基乙酸 NDN- N,N-(二氨基魷甲基)氨基乙銑基NDNt u- N,N-(二叔丁氨基銑甲基)氨基乙酸 P 3-毗咬丙氨酸 NTA - N,N-(dioctyloxycarbylmethyl)aminoacetic acid NDN- N,N-(diaminofluorenylmethyl)aminoethyl milling NDNut u- N,N-(di-tert-butylaminomethyl) Glycine P 3-azetyl alanine

Phe- 苯丙氨酸， Phe- phenylalanine,

RP-HPLC- 反相高效液相色借 RP-HPLC- reversed-phase high-performance liquid chromatography

PIo-SeI- TEA- 三乙腰 e doPIo-SeI- TEA- triple waist e do

p p

he( ) (( , ) ) He( ) (( , ) )

he( ) (( 氧碳 ) ) He( ) ((oxygen carbon) )

Fhe( ) (( , 氨基 ) ) Fhe( ) (( , amino ) )

he( t u ) (( , 氨基 ) ) he( ) (( , 二楚 ) ) He( t u ) (( , amino ) ) he( ) (( , 二楚 ) )

he( ) (( 氧 ) ) 除非另有在本中使用的木具有以下。 He( ) ((oxygen)) Unless otherwise used in this wood has the following.

本明中，所有氨基酸注明外，均力。 " "是或其中的本文中。 In the present specification, all amino acids are indicated, and the same is true. " " Yes or one of them in this article.

" 氨基"是指，其中的本文中。 " 氧基碳 "是指，其中的本文中。 "Amino" refers to the text in which it is. "Alkyl carbon" refers to the text of this article.

性的氧基碳包括氧基碳基和氧基碳。除非另外， " "是指直或的中具有約 1 約碳原子的其介或素原子取代。中具有 1 碳原子的更化健中具有 1 碳原子的。作力介基因或低氧基、低、低亞硫或低等的組成部分的 "低 " 是指直或的中具有 1 碳原子的，除非外。性的包括、、、、 The oxycarbons include oxycarbyl and oxycarbon. Unless otherwise specified, "" refers to a substitution of a meso or alkene atom having about 1 about a carbon atom in a straight or a straight. The more normal one with 1 carbon atom has 1 carbon atom. A "low" that is a component of a gene or a low oxy group, a low, a low sulphur, or a low component refers to a straight one or one carbon atom unless otherwise. Sexuality includes , , , , ,

、、、、、辛基、、基和十二。介或素原子取代的的包括。可以 1 、、或立地自鹵素，硝基，氨基，，，或氧基或者 , , , , , , 辛基 , , Base and twelve. Substituted by a medium or a substituted atom. May be 1, or, or from a halogen, nitro, amino, , or oxy group or

的取代取代。 Replacement of the substitution.

" "是指含有碳碳同中具有約約碳原子的直或的。中具有 1 碳原子的，更中具有碳原子例碳原子)。在此和文本中所用的 "支鏈" 是指介或低、或連接在直上在此是指直。 "低 " 是指中含有約約碳原子，其可以是或的。 "" means a straight or a carbon-carbon having approximately a carbon atom. It has 1 carbon atom and has a carbon atom in the middle. The term "branched" as used herein and in the text refers to either "low" or "directly" or "directly connected". "Low" means that it contains about a carbon atom, which can be or .

性的包括乙烯、丙烯、、、 Sexuality includes ethylene, propylene, , ,

、、、、基和。可以可以 1 、、或立地自素硝基，氨基，，或氧基或者的取代取代。 , , , , , and . It may be substituted with 1, or , or a substitution of a nitro group, an amino group, or an oxy group.

" "是指含有碳碳，同是直或的中具有約約碳原子的。的在中具有 1 碳原子和更中具有碳原子(例碳原子)。 "" means carbon-carbon, which has about or about a carbon atom. It has 1 carbon atom and more has a carbon atom (for example, a carbon atom).

性的包括、、、、 Sexuality includes , , , , ,

基和。可以 1 、、或立地素，硝基，氨基，，，氧基或者的取代取代。 Base and . It may be substituted by 1, or , or a nitro, amino, , or oxy group or a substitution.

" 氧基" 是指 0 ，其中的本文中。氧基的包括氧基、氧基、氧基、氧基、氧基、氧基、氧基和氧基。 "Oxy" refers to 0, which is in this article. The oxy group includes an oxy group, an oxy group, an oxy group, an oxy group, an oxy group, an oxy group, an oxy group and an oxy group.

" "是指，其中的本文中。 " 氧基"是指 0 ，其中上。的氧基包括氧基。 "" means, among them in this article. "Oxy" means 0, which is above. The oxy group includes an oxy group.

" " 是指，其中上。 " " means , which is above.

" 素" 包括、、和，、或。 "素" includes , , , and , , or .

" " 是指，其中的本文中。性的包括苯甲， 1 基和。 "" refers to , among them in this article. Sex includes benzene, 1 base and .

" 氨基"是，其中上。 "Amino" is , which is above.

" "作力介基因或基因的組成部分代表 ) 1 碳原子的取代的羊或族碳杯部分，苯基或或( ) 取代的部分飽和的族碳杯部分，其中基和或合在起，例氧、或氫。除非另外，可以介或 ( 、、、 ) 取代取代，其可以相同或不同，其中 "芳基取代 " 包括，例、氨基、氧基、氧基碳二氧基、亞硫、、、、氨基、、氧基、氧基碳、 "" is a component of a gene or gene that is represented by a component of a carbon or a substituted carbon or a portion of a carbon or a cup, a partially saturated saturated carbon cup portion substituted with a phenyl group or ( ), in which a group and a group are combined, For example, oxygen, or hydrogen. Unless otherwise, the substitution may be substituted by ( or , , , ) which may be the same or different, wherein "aryl substituted" includes, for example, amino, oxy, oxycarbodioxy, sulfite, , , , amino, , oxy, oxy carbon,

、氧基、氧基碳亞硫、、、 (或生物等 )、、素、、、氧基、氨基、氧基、、硝基、、，例素，硝基，氧基，氧基，，亞磺，，氧碳，氨基，氨基，氨基或 , oxy, oxycarbosulfide, , (or biological, etc.), aryl, aryl, hydroxy, amino, oxy, nitro, nitro, nitro, oxy, oxy, Sulfin, oxycarbon, amino, amino, amino or

碳氨基。 " 取代 " 中的基因具有本明中出的。 Carbon Amino group. The genes in "replacement" have the ones in this book.

" 氧基" 是指 0 ，其中上。性的氧基包括氧基和 1 氧基或氧基。 " "是指，其中的如上。性的是。 "Oxy" means 0, which is above. Alkoxy groups include oxy groups and 1 oxy or oxy groups. "" means that, among them. Sex is.

" 氧基"是指G基 0 ，其中上。性的氧基包括氧基和氧基，其各任取代。 "Alkyl" means G group 0, of which is above. The oxygen group includes an oxy group and an oxy group, which are each substituted.

" "是指含有至少介碳碳具有約約 1 碳原子的非羊或杯杯。性的羊杯杯包括 " " means a non-sheep or cup containing at least about 1 carbon atom. Sexual sheep cups included

、基和。可以 1 、、或立地自素，硝基，氨基，，或氧基的取代取代。 , base and . It may be substituted by 1, or , or by a substitution of a nitro group, an amino group, or an oxy group.

" "是指 1 碳原子的飽和羊或杯杯 " " means a saturated carbon or cup with 1 carbon atom

氧取代。性的羊杯杯包括，，，、、基和。可以 1 、或立地素，硝基，氨基，，， Oxygen substitution. Sexual sheep cups include , , , , , and . Can be 1, or genomic, nitro, amino, , ,

或氧基的取代取代。Or a substitution of an oxy group.

" "是在其中具有介或多 ( 、、、 ) 原子的化合物。的原子包括氮( )、氧(0)和 (5)。基特別可以是的 (也就是 )、飽和的或部分飽和的。本化的羊包括勻羊。 " " is a compound in which there are intermediates or poly ( , , , ) atoms. The atoms include nitrogen ( ), oxygen (0) and (5). The base can be (ie), saturated or partially saturated. The natural sheep include the uniform sheep.

和族化合物近可步下基因取代素，氧基，，氧基，硝基，氧基，氨基或苯基。 And the compound is close to the gene replacement, oxy, oxy, nitro, oxy, amino or phenyl.

本的或的包括 1 ，或 1 ，、、、 1 ，、 1 The sum of this includes 1 , or 1 , , , , 1 , , 1

1，或 1，，、 1，，或 1，，，二吐、、、 1，，、或、、 1 或、、或、 -3- -4-或_ _基、 1，2,3-> 1，2 1，2 5 或 1， 3,4-嗯二 _ _ 哇、 -4-或-5-基、嗯四湊基、嗯三嗓基、 1，2， 3，4-或 1，2， 3，5-嗯三哇基、嗯 9 -4-或-5-基、 2-或 3-毗嗓基、 1- 3-或 4-毗哇基、 3-或 4-吱嘻基、 3-或 4-毗咬基、 2- 4-或 _喀咬基、1, or 1, , , 1, , or 1, , , two spit, , , 1, , , or , , 1 or , , or -3- -4- or _ _ base, 1,2,3-> 1,2 1,2 5 or 1, 3,4- um two _ _ wow, -4- or -5-base, um Base, umsan, 1, 2, 3, 4- or 1, 2, 3, 5 - um, three wu, y, 9 or -4-, ke, 2- or 3-pyryl, 1 3- or 4-pywayl, 3- or 4-mercapto, 3- or 4-pyrylene, 2- 4- or _ carbyl,

2 或 3-毗咯基、 1，2， 3，4-或 2， 1， 3，4-四哇基、喀二哇-3- -4- 或喀哇-2- -4-或-5-基 2-或吩基、 1，2,3- 1，2,4- 或 1， 3,5-三嗓基和 1，2 1，2 2， 1,3-或 4， 1,2-三哇基。本友明最仇迭的芳族奈杯基包括吠喃-2-基、吠喃-3-基、 2- 4- 或 5-咪哇基、 3- 4-或 _弄嗯哇基、 2-或 3-毗咬基和 1-或2-喀吩基。 2 or 3-pyrrolyl, 1,2, 3,4- or 2, 1, 3,4-tetrawayl, Kawarwa-3--4- or Kawa-2--4- or -5 -yl 2 or phenyl, 1,2,3- 1,2,4- or 1,3,5-trimethyl and 1,2 1,2 2, 1,3- or 4, 1,2- Three wow base. Ben Youming's most capricious aromatic nai cup base includes 吠-2-yl, 吠--3-yl, 2- 4- or 5-imicy, 3- 4- or _ 嗯哇哇, 2 -or 3-didentate and 1- or 2-carbo.

本友明化迭的飽和或部分飽和或 6-元染杯基的奕例包括 1， 3，5，6，2-二嗯二湊基、 1，2， 3，4， _或 1，2， 3，5，4-二嗯二哇基、二嗯燒基、 1， 3-二氧柴杯戊烯基、 1， 3，5，6，2-二嚷二嗓基、 1，2， 3,4,5-或 1，2， 3，5，4-二喀二咄基、 2-弄咪哇基、弄毗咯基、弄四哇基、1，2， 3-或 1，2，4-弄三哇基、嗎琳基、嗯二嗓基、1，2，4- 1，2，6-、 1， 3，2-、 1， 3，6-或 1，4，2-嗯嘻基、呱嗓基、高呱嗓基、呱咬基、 1，2-、 1， 3-或 1，4-毗喃基和 1，2， 3-毗咯燒基。 Examples of saturated or partially saturated or 6-symbolized cup bases of this friend include 1, 3, 5, 6, 2, 2, 2, 2, 3, 4, _ or 1, 2 , 3,5,4- 嗯二哇哇二二二二二二二、、、、、、、、、、、、、、、、、 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 2, 3,4,5- or 1,2,3,5,4-di-carbyl, 2-mimi-m, pyridine, sulphate, 1,2, 3- or 1,2 , 4-made three wow, morphine, um dimercapto, 1,2,4- 1,2,6-, 1, 3,2-, 1, 3,6- or 1,4,2-嘻嘻, 呱嗓, 呱嗓, 呱, 1,2-, 1, 3- or 1,4-pyranyl and 1,2,3-pyrrolidyl.

"柴杯燒基"是指: (i)約 3-8元杯的杯燒基，其含有介或多介染原子或迭自 0、 S和 NR R'的含染原子基因井且可以任卜迭地被氧取代; (ii)部分飽和的多杯含朵原子碳杯部分，其中芳基(或染芳基)杯，分別任迭地被介或多介 "芳基取代基"取代，井且朵杯燒基稠合在一起枸成杯卜狀結枸 (此矣基因的奕例包括苯井二氫毗喃基，二氧苯井吠喃基，二氫叫味基和毗咯井[ ,2-a]毗咬基 "Chai Cup Burning Base" means: (i) a cup-burning base of about 3-8 cups containing a medium or a multi-dye atom or a dye-containing atomic well from 0, S and NR R' Substituted by oxygen; (ii) partially saturated multi-cup containing a portion of the atomic carbon cup, wherein the aryl (or aryl) cup is replaced by an intervening or poly-"aryl substituent", The well and the cup-burning base are condensed together into a cup-shaped knot. (Examples of this gene include benzene dihydropyridyl, dioxanthene, dihydrogen and pyrrole [ , 2-a]

根搪本友明，式( ) 「肢衍生物及其立休弄枸休和其元生理毒不在激素分泌中良好效果，而且在休外測定中較低的組，因此可作力激素于，于哺乳特別是。搪本本明明,式() "The limb derivative and its stagnation and its metaphysical toxicity It does not have a good effect in hormone secretion, and it is a lower group in the measurement of rest, so it can be used as a hormone, especially for breastfeeding.

本因此涉及含有作力活性成分的有效量的至少 Therefore, it relates to an effective amount containing at least a working active ingredient

1) 衍生物和/或休休或生理毒性以及常規賦形或的物組合物。 "常規賦形或 " 包括任或所有，分散，或，等及，以及似的生理配伍，以合注射，肌肉注射，皮下注射或其它方式。的方式，可將性化合物以化合物兔或其它然余的影而。 1) Derivatives and/or rest or physiological toxicity as well as conventional shaped or composition compositions. "Regular shaping or" includes any or all, dispersion, or, etc., and similar physical compatibility, in combination with injection, intramuscular injection, subcutaneous injection or other means. The way, the sex compound can be seen as a compound rabbit or other.

本所用木 " 生理毒性的 " 是指可保留休化合物預期生理活性而不戶生任何意料外副作用的或者它們的合物。例，氫，硫酸，磷酸，硝酸以及醋酸，草酸，，，苯甲，，海藻，磺酸，磺酸等。中含有的子又可，，，，，，等可等有。 The term "physiologically toxic" as used herein refers to a compound which retains the expected physiological activity of the compound without any unanticipated side effects or compounds thereof. For example, hydrogen, sulfuric acid, phosphoric acid, nitric acid and acetic acid, oxalic acid, , , benzoic acid, seaweed, sulfonic acid, sulfonic acid, etc. The sub-containing can be , , , , , , etc.

本十衍生物或休休或生理毒性或含有它的物組合物可以以已知的任何方式，口服、肌肉、皮下等，給例、、、嚼、、、、微東、、等。可以是普通制、、及各科微粒統。了將羊 The ten derivative or the composition of the resting or physiological toxicity or the composition containing the same may be administered orally, muscle, subcutaneously, etc. in any manner known, for example, chewing, , , , , , , , , . It can be general system, and various micro-organisms. The sheep

，可以使用本領域的各科生物可的或生物相容休。于休的例子，如水及各沖水溶液、乙醇或其它元、休、乳酸、乙烯、、、等。 , can be used in various fields of the field biocompatible or biocompatible. Examples of Yuxi, such as water and various aqueous solutions, ethanol or other elements, Hugh, lactic acid, ethylene, , Wait.

本 (1) 衍生物或休休或生理毒性的取決于因素，例如所要預防或治行疾病的性和程度，患者或物的性別、年齡、休，敏感性及休反，所用的休化合物，給往，給以及希望到的效果等。上可以羊形式或分成，例二、三、形式。羊最大般不 g/ g休例如． 1 g/ g休， 1 g/ g休，較佳固． 9/ 9休。但是，在某些情況下，也可能使用 g/ g 休以上或者 g/ g休以下的羊。 The (1) derivative or resting or physiological toxicity depends on factors such as the nature and extent of the disease to be prevented or treated, the sex or age of the patient or the substance, the sensitivity, and the reversal of the compound used, We give, and we give effect to hope. It can be in the form of sheep or divided into two, three, and three forms. The sheep are not as big as g / g . 1 g / g rest , 1 g / g rest , better solid . 9/9 off. However, in some cases, it is also possible to use g/g or above or g/g for the following sheep.

下面的及生物活性未步明本，但不意味看本的任何限制。 The following and biological activities are not available, but do not imply any limitations of this.

所用固相合成休天津南合成責任有限公 B B 以及 oc 休的天然氨基酸由上海生化公以及成都新木有限責任公， Boc 的非天然氨基酸外均由本合成提供。 1 , ( 氧碳 ) 氨基 [ ]的合成二乙 ( . o1, 9) (1. 1， 9) 于 1 中， L 乙醇溶解。下 The solid phase synthesis used in Tianjin Nanbei Synthetic Responsibility B B and the natural amino acids of oc Hugh are provided by Shanghai Biochemical Co., Ltd. and Chengdu Xinmu Co., Ltd., and Boc's unnatural amino acids are all provided by this synthesis. 1 , ( Oxycarbon) Synthesis of Amino [ ] Diethyl ( . o1, 9) (1. 1, 9) In 1 , L ethanol is dissolved. under

1 L, o ) 室溫，乙醇，水溶液至，再水相至酸性，萃取，水兩次，以水硫酸。， 1 L, o ) room temperature, ethanol, aqueous solution to, then aqueous phase to acidic, extracted, water twice, with water sulfuric acid. ,

得 9 ， . L 氯仿 c( 1 . ), . 。氧碳二乙酸的合成Get 9 , . L chloroform c ( 1 . ), . . . Synthesis of oxycarbodiacetic acid

. g( . o1) 二乙， L水, L 的 , L二氧。 p ， 1. g(Boc) 0( . o1，于 L二氧 )。反中保持， 1 除去二氧，水相萃取酸化至 p ，萃取，氯仿萃取。，，得 1. 9白固休。． 1 g( . o1) Diethylene, L water, L, L dioxane. p , 1. g(Boc) 0( . o1, in L dioxin). In the opposite, 1 removed the dioxane, the aqueous phase was extracted and acidified to p, extracted, and extracted with chloroform. , , got 1. 9 white solid rest. . 1

= .5 水, ), p. 1 1 C。氧碳二乙的合成 = .5 water, ), p. 1 1 C. Synthesis of oxycarbon diethylene

1 9( . o ) 氧碳二乙于 L 水氫中， 1 C下 . L ， 1 9 ( . o ) Oxygen - carbon dichloride in L water hydrogen , 1 C lower . L ,

. L ( . O ) ，， . L( . o1) 。 L ，原料已反。 L ( . O ) , , . L( . o1) . L, the raw materials have been reversed.

氫，，去不，分別碳酸氫水，水，酸水飽和食水水硫酸。，石油。得白固休 1. 19， . . ( Hydrogen, , go, respectively, hydrogen carbonate water, water, acid water, saturated water, water, sulfuric acid. , oil. Get white and rest 1.19, . . (

1 . ), ．p. 1 1 1°C。 1 . ), . p. 1 1 1 °C.

二乙的合成 Synthesis of diethyl

g ( . o ) 氧碳二乙于 1 L / t c溶液中， 1 L ，原料已反。 g ( . o ) Oxygen carbon Diethyl in 1 L / t c solution, 1 L, the raw material has been reversed.

，得 9白固休 . ( 氨基 ) 氨基 [ "]的合成． 9 ( o1)的二乙于 L二氧杯中，． L( 0 O )的，生成的，． 9 (1 o1) 。 C 熱反，，， L水，酸化至 p ，用水，飽和水水硫酸。，，得 1． 9 白固休。 .1 。．p． 1 1 C, TL ( , get 9 white solids. (Amino) amino [ [] synthesis . 9 ( o1 ) of the second in the L dioxygen cup, . L( 0 O ), generated, . 9 (1 o1). C heat reverse, , , L water, acidified to p, water, saturated water sulfuric acid. , , got 1. 9 White solid rest. .1 . . p. 1 1 C, TL (

水, 1 ) . 。 Boc p he的合成 Water1 ) . . Synthesis of Boc p he

c he(p ) he (本按照常規方法制各， ( 9, 1. o1)于 L 和 L二氧杯中回流 1 > 蒸去和二氧，得到固休不化直接在下 L ，至，再． o1 .g L), 然． 9 (Boc) 0 ( 1.1 O ) 室溫 1 c he(p ) he (This method is prepared according to the conventional method, (9, 1. o1) is refluxed in L and L dioxygen cups 1 > evaporated and dioxin, which is obtained directly under L, to, and then .o1 .g L), of course. 9 (Boc) 0 ( 1.1 O ) room temperature 1

水溶液至酸性，萃取，水兩次水硫酸。，石油結晶得． 9 白休， .1 L 氯仿 Aqueous solution to acid, extraction, water twice water sulfuric acid. The oil crystallizes . 9 white, .1 L chloroform

c( 1 . ) . 。氧碳 ( 氧碳 ) c( 1 . ) . Oxygen carbon (oxygen carbon)

[Boc Phe( ) 的合成 Synthesis of [Boc Phe( )

1. 9 ( o ) Boc he . 9 (1 o1) 二乙和 F混合，回流反 h。水 1. 9 ( o ) Boc he . 9 (1 o1) Diethyl and F are mixed and refluxed with h. Water

，萃取。飽和 a ，水硫酸。， ( 石油， 1 1 1)。 , extraction. Saturated a, water sulfuric acid. , (oil, 1 1 1).

，溶解碳酸氫水，酸水，飽和水，水硫酸。，石油。，得白固休 1． g9(常溫下，冰涼固休)， . TL ， . (氯仿， 1 . ). 氧碳 (NN 氨基 ), dissolved hydrogen carbonate water, acid water, saturated Water, water sulfuric acid. , oil. , got the white solid holiday 1. G9 (under normal temperature, cold and solid), TL, . (chloroform, 1 . ). Oxygen carbon (NN amino)

[ oc he( u ) ]的合成 Synthesis of [ oc he( u ) ]

將 1. 9 ( o1) Boc Phe 1. 9 (. o1) 二乙、． L( . o1) 和 L 混合，熱 C ，反。停止反蒸去水，酸化至。萃取。飽和食水水硫酸。，，石油。，得白固休． 9， TL ， . (氯仿 Will be 1. 9 ( o1 ) Boc Phe 1. 9 (. o1) . L( . o1) and L are mixed, hot C, and reverse. Stop de-steaming and acidify to acid. extraction. Saturated water, water, sulfuric acid. , , Oil. , get white and rest . 9, TL, . (chloroform

1 . ) p. °C。氧碳二乙醇的合成 1 . ) p. °C. Synthesis of oxycarbon diethanol

1. 9 (1 o1) 二乙醇， L水 L a L二氧。控制 p ， . 9 (1 o1) (Boc) 0( 于 L二氧 )。反中休， 1 除去二氧，水相萃取酸化至，萃取萃取。，，得 1. 9 。 . , . 1(氯仿， 1 . ) 1 氧碳二乙基辛的合成 1. 9 (1 o1) diethanol, L water L a L dioxane. Control p , . 9 (1 o1) (Boc) 0 (in L dioxin). Anti-offset, 1 removes dioxane, extracts acid phase from aqueous phase, extracts and extracts. , , got 1. 9 . . , 1 (chloroform, 1 . ) 1 Synthesis of oxycarbon diethyl octane

1 9 ( O )的氧碳二乙醇于 L T F 中， 1 C下分批 g9 (1 . o )的 a ，． 9 ( . o1) 化和 1. L (1 . o1) 化， L 原料已反， L水水解， T F L 水，萃取，水，飽和食水，水硫酸。 1 9 ( O ) of oxycarbon diethanol in LTF, batching g9 (1 . o ) at 1 C. 9 ( . o1) and 1. L (1 . o1), L raw material has been reversed, L water hydrolysis, TFL water, extraction, water, saturated water, water sulfuric acid.

，石油， 1 )得 1.1 9 。 , oil, 1) got 1.1 9 .

. , . 1( )。 11 二乙基辛的合成 . , . 1( ). Synthesis of 11 diethyl octyl

1.1 9( .1 o )的氧碳二乙于 1 / t c溶液中， 1小 L ，原料已反。 1.1 9 ( .1 o ) of oxycarbonate in a 1 / t c solution, 1 small L, the raw material has been reversed.

，得 1. 9白固休 . 氧碳 ( 氧 , get 1. 9 white solid rest. Oxygen carbon (oxygen

[Boc he( ) ]的合成 Synthesis of [Boc he( ) ]

.1 9 . o1) Boc Phe . 9 .1 o1) 二乙千、． L( . o ) 和 L 混合熱 C ，反。停止反，蒸去，水，酸化至。萃取。飽和食水，水硫酸。，， (氯仿， 1 . )得． 9 。 1. , . (氯仿 .1 9 . o1) Boc Phe . 9 .1 o1) Two thousand thousand , . L( . o ) and L mixed with heat C, inverse. Stop the reverse, steam, water, acidify to. extraction. Saturated water, water sulfuric acid. , , ( chloroform , 1 . ) 9 . 1. , . (chloroform

1 . ). 1 " 氧碳千 1 . ). 1 " Oxygen carbon thousand

[Boc Ly (Bz ) ]的合成Synthesis of [Boc Ly (Bz ) ]

L反內 Boc Ly ( ) . 9, 1 P . 9, L 水， kg/c ，溫度 C，反 h。，下 L 苯甲， 9 1 d 和 L 水， kg/c ，溫度 C反 h。，走，下 L ，，下飽和 a ， p ，萃取余的苯甲，水相酸調，萃取合井相，水，L anti-inner Boc Ly ( ) . 9, 1 P . 9, L water, kg/c, temperature C, anti-h. , L L benzo, 9 1 d and L water, kg / c, temperature C anti h. , go, down L , , lower saturation a , p , extraction of residual benzene, aqueous acid adjustment, extraction of well phase, water,

)。，結晶，得白固休 9， . TL ， = . (氯仿 ). , crystallization, whitening, solid, 9. TL, = . (chloroform

, 1 1). 1 " 氧碳氧碳辛基 , 1 1). 1 " Oxycarbon Carbon Oxygen Octyl

[Boc Ly (Bz F oc) ] [Boc Ly (Bz F oc) ]

Boc Ly (Bz ) ( . 9, . o1)溶解于 1 0中， a 溶液 p 1 , L ox L ox 溶解 F oc u( . 9，． 1 1． )，緩慢加休，羊，保持常溫下反。走 o ，水至 L 萃取， p ， Boc Ly (Bz) ( . 9, . o1) is dissolved in 10, a solution p 1 , L ox L ox dissolves F oc u ( . 9, . 1 1. ), slowly increases rest, sheep, keeps at room temperature anti. Go o, water to L extraction, p,

萃取，合井相，飽和 a ，水硫酸。，， 1)，得，石油固休，水 / 結晶，得． 1 9。．。 L ， . (氯仿醋酸， 1 . ). 1 " 氧碳 ( 氧碳 )Extraction, well phase, saturation a, water sulfuric acid. , , 1), get, oil, rest, water / crystallization, get. 1 9. . . L , . ( chloroform acetic acid , 1 . ) . 1 " oxygen carbon ( oxygen carbon )

[ oc p(F oc) ] [ oc p(F oc) ]

下往 L 水中， n，使到飽和。 1 L d Z 溶解 Boc he ( 9, . o1),分批飽和 / e 中，保持，度及低溫余下反 h以上，監測(氯仿醋酸， 1 . )反完全 Down to L water, n, to saturate. 1 L d Z Dissolve Boc he ( 9, . o1), batch saturation / e, hold, degree and low temperature residual anti-h or more, monitor (chloroform acetic acid, 1 . )

，常溫，，得固休直接于下步反。 L . ( 醋酸水， 1 1). 將上步反所得溶解于 L水中，下 1 a ， p ， L二氧， L二氧溶解 F oc . 9，． )，休。下反，常溫反。 L水，萃取 , normal temperature, , Deguxiu directly in the next step. L. (Acetic acid water, 1 1). The upper step is dissolved in L water, the lower 1 a, p, L dioxane, L dioxygen dissolved F oc . ), Hugh. Reverse, normal temperature is reversed. L water, extraction

下酸調 p ，萃取，合井相，依次用水，飽和 a ，水硫酸。，， ( Et c, 1 1 前端 e c, 1 ． )。 Under acid adjustment p, extraction, well phase, followed by water, saturated a, water sulfuric acid. , , ( Et c, 1 1 front end e c, 1 . ).

，得固休 1． 9。 . TL f ． (氯仿醋酸， 1 . ) 1 化合物(1 )的合成 , have a fixed time 1. 9. TL f . (chloroform acetic acid, 1 . ) 1 Synthesis of compound (1)

以 ( . o1) 固相休， B / 合，化合物的氨基酸序列，的 Boc 固相合成方法 (參考惟著，合成，出版社， 1 ) 操作合成 c a pa he e n op Leu g o a B 。 The solid phase synthesis of (.o1), the B/H, the amino acid sequence of the compound, and the Boc solid phase synthesis method (cf., synthesis, press, 1) operate to synthesize c a pa he e n op Leu g o a B .

將上放 F切割的反器中， 1． L苯甲，裝好特 F切割的休，氮反， Will put the F-cut counter, 1. L benzophenone, loaded with special F-cut Hugh, nitrogen counter,

1 L F，于 C反。用油泵抽走 F，取下反，水固休再將特移至漏斗中。少量的元水三次，再用 1 的酸水溶液沖洗至不再相互，收集，得 . 9白，1 L F, in C reverse. Use the oil pump to remove F, remove the reverse, and then move the water to the funnel. A small amount of water is used three times, then rinsed with 1 acid aqueous solution until they are no longer collected from each other. 9 white,

. 。 P L 化得 1. . . . P L is 1.

B 1 . ( 1 .1). 1 大休抑制作用 B 1 . ( 1 .1). 1 big break inhibition

前休，玻璃毛細管，血清用化學友光法測定血清含量，含量和休隨和分組只，分別于次皮下注射或化合物(不同 ) 、1 等，， p Q n 將得到的血清用化光法 ( eck an ou te 公 cce unoa ay y te 化 )測定血清含量。 1 促使大腹腔肥大細胞的能力測定只雄性大放血，腹腔注射 B L/只，腹腔腹腔至中 1 p 1 ， Premature vaccination, glass capillary, serum by chemical light method for determination of serum content, content and rest and grouping only, subcutaneous injection or compound (different), 1, etc., p Q n will be obtained by using the sera ( eck an ou te public cce unoa ay y te)) Determination of serum content. 1 The ability to induce large abdominal mast cells is measured by male bloodletting, intraperitoneal injection of B L / only, abdominal cavity to the middle 1 p 1 ,

次合井細胞，將羊細胞，細胞稀釋倍有細胞。上細胞分別不同的 C 有 1 ，煮沸終止反。 In the secondary well cells, the sheep cells and cells are diluted with cells. The upper cells have different C, and the boiling stops.

上 B 公的化于 E n E n 測定強度強度的百分率， The upper B is converted to the percentage of intensity strength measured by E n E n ,

物的 E E

a 皮下 ug/ g b 服 1 g/kg a subcutaneous ug/ g b serving 1 g/kg

# B 太高 # B too high

> 未到抑制活性 > no inhibitory activity

Claims

要求 1． (U「tk衍生物或休休或生理毒性， pa aa e aa， a a ' a o a 其中，Requirements 1. (U "tk derivative or resting or physiological toxicity, pa aa e aa, a a ' a o a

( ) ( ) ( ) ( ) 、 P( ) ( ) ( ) ( ) ( ) > ( ) ( ) ( ) ( ) ( ) ( ) , P( ) ( ) ( ) ( ) ( ) > ( ) ( )

( ) ( )

、，、，和相互立地分別，含有或不含有 , , , , and mutually separate, with or without

、磷酸、的取代或未取代的，直或 , substituted or unsubstituted, phosphoric acid, straight or

取代或未取代的，，直或或者，取代或未取代的，直或氧基，取代或未取代的，直或 Substituted or unsubstituted, straight or or, substituted or unsubstituted, straight or oxy, substituted or unsubstituted, straight or

，取代或未取代的，直或，取代或未取代的，，直或氧基或者氧基，取代或未取代的，，直或或者，取代或未取代的，直或或者，或 ( ，) ， Substituted or unsubstituted, straight or substituted or unsubstituted, straight or oxy or oxy, substituted or unsubstituted, straight or or substituted or unsubstituted, straight or or, or (,) ,

( ，) ， ( ，) ， ( ，或 ( ,) , ( , ) , ( , or

其中、、磷酸、是介或 p 分別立地連接在、，、和的任何介碳原子上 Wherein, phosphoric acid, mediated or p are respectively attached to any of the carbon atoms of , , , and

t、 n和 p分別立地的 T, n, and p respectively

， ( ), ( ), ( v)或(v)

, ( ), ( ), ( v) or (v)

立地的 Site

，和，，相互立地分別取代或未取代的，直或，取代或未取代的，，直或或者，取代或未取代的，直或氧基取代或未取代的，直或，取代或未取代的，直或 , and, respectively, substituted or unsubstituted, straight or substituted or unsubstituted, straight or or substituted or unsubstituted, straight or oxy substituted or unsubstituted, straight or substituted or unsubstituted Direct or

，或 ( ，) ， ( ，) ， ( ，) ， ( ，) ， q 立地的 , or ( , ) , ( , ) , ( , ) , ( , ) , q

、 c ( 、 D E nanthy 、 Laury 、 Pa y 、 Bu y y 、 cot noy 、 Pe a gony n > p pe y 、 o pho ny 、或 t B g ， , c ( , D E nanthy , Laury , Pa y , Bu y y , cot noy , Pe a gony n > p pe y , o pho ny , or t B g ,

，相互立地分別、取代或未取代的，直或 " Reciprocal , substituted or unsubstituted, straight or "

取代或未取代的，，直或或者 Substituted or unsubstituted, , straight or or

或未取代的，直或氧基，取代或未取代的直或，取代或未取代的，直或，或 ( ) ， ( ，) ， ( ，) ， Or unsubstituted, straight or oxy, substituted or unsubstituted straight or substituted or unsubstituted, straight or Or ( ) , ( , ) , ( ,) ,

( ，) 或 , q 立地的整數，例如 0， 1，，，，或 ( ,) or , q an integer of the place, such as 0, 1, , , , or

， aa P e或 P aa , aa 和 aa 各立地 L 或型的 Ph ( )> he( ) phe( ) ph( c) op phe ph p ph g> o u p n n Ly y n o n t 或者 ph中的任何 , aa P e or P aa , aa and aa each of the L or type of Ph ( )> he( ) phe( ) ph( c) op phe ph p ph g> o u p n n Ly y n o n t or any of ph

或者 or

aa , aa 或 aa 相互立地力以下 ( )或 (1 1)的 Aa , aa or aa stand below each other ( ) or (1 1)

> ( ) ( ) ( ) ( ( ) ( ) ( ) ( ) ( ) ( )P( ) ( ) "或

> ( ) ( ) ( ) ( ( ) ( ) ( ) ( ) ( ) ( )P( ) ( ) " or

> ( ( ) > ( ( )

( ) 、 ( ) 或 ( ), ( ) or

立地的整數相互Site integer Mutual

" " 立地分別 ( ) 、， (0) ，， ( ) ，其中，，和，分別，取代或未取代的直或，取代或未取代的，直或或者，取代或未取代的 0直或氧基，取代或未取代的，直或，或 ( ，) ， " " , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Base, substituted or unsubstituted, straight or, or ( ,) ,

( ，) ， ( ，) ， ( ，) ，或， n 立地的 ( , ) , ( , ) , ( , ) , or , n

aa化 he( ) he( ) phe( )> ph( c) op he ph p P o ph g n n u p phe( ) 或 h ( ) Aaization he( ) he( ) phe( )> ph( c) op he ph p P o ph g n n u p phe( ) or h ( )

aa he( ) he( ) he( ) ph( c) o p op he ph ph g n n u p h ( ) he( ) ph(Lau y ) D p ( a y ) D p (Buty y ) ph( cot noy ) p ( e a gony ) ph( ) ph n P ) p (P pe dy 、 ph( o pho ny ) ph( P ) ph( E ) Aa he( ) he( ) he( ) ph( c) op op he ph ph gnnuph ( ) he( ) ph(Lau y ) D p ( ay ) D p (Buty y ) ph( cot noy ) p ( ea gony Ph( ) ph n P ) p (P pe dy , ph( o pho ny ) ph( P ) ph( E )

aa化 g Ly n n或 n 和 aa Leu, c 或 c 其中，中 1 ( 1 ) 立地、和的原子的基因未取代的或立地自素，硝基，或的取代羊取代或取代或取代的、、或羊或芳香基因，苯基或者未取代的或立地自鹵素，硝基，或的取代羊取代或取代的、含有 1 立地自、和的原子的、、或羊或芳香基因， Aa of g Ly nn or n and aa Leu, c or c wherein, 1 (1) of the site, and the atom of the gene is unsubstituted or substituted by a nitro group, or a substituted sheep, substituted or substituted, , or sheep or aromatic gene, phenyl or unsubstituted or standing from halogen, nitro, Or substituted or substituted, containing, or a sheep or an aromatic gene,

，，。．要求 1 的 (1)十衍生物或休休或生理毒性 aa， aa或 aa相互立地力以下 ( )或 1 ) 的 , , . . Requires 1 (1) of the ten derivatives or rest or physiological toxicity aa, aa or aa mutual standing force () or 1)

( ) - ( ) ) > ( ( ) ( ) ( ) ( )P( ) P( ) " (

( ) 6 ( ) 9 0) 、 (0) ( ) 6 ( ) 9 0) , (0)

立地的整數 Site integer

相互 mutual

" " 立地分別 0 、， ( ) " " Sites 0 , , ( )

( ) ，其中，和，分別，取代或未取代的，直或，取代或未取代的，直或或者，取代或未取代的，直或氧基，取代或未取代的，直或，或 ( ，) ， ( ), where, and, respectively, substituted or unsubstituted, straight or substituted or unsubstituted, straight or or, substituted or unsubstituted, straight or oxy, substituted or unsubstituted, straight or, or ,),

( ，) ， ( ) ， ( ，) 或， n 立地， 1，，或。 3 - f; J- -- -- - - -- - - -. -#-4cM-' i.( ,) , ( ) , ( , ) or , n Site, 1, , or . 3 - f; J- -- -- - - -- - - -. -#-4cM-' i.

--*#1J&2 (I)tWi i --*#1J&2 (I)tWi i

-- -- - - -- M) -- -- - - -- M)

- -? - (-l)-Ac D-Nal' D Cpa D Pal Ser Arg D Pal Leu Arg P s ro D Al 10 - -? - (-l)-Ac D-Nal' D Cpa D Pal Ser Arg D Pal Leu Arg P s ro D Al 10

a NH a NH

(2)NH CO D Na D Phe Ser Arg (2) NH CO D Na D Phe Ser Arg

0 rD Cpa D Pal Leu Arg 9 0 rD Cpa D Pal Leu Arg 9

Pro D A Pro D A

(3)N-l 1 (3) N-l 1

a a

H -NH- N -- - - -- - -6 - - - - CO D al' D Cpa D Pal Ser Arg D Pal Leu Arg Pro D Al 10 H -NH- N -- - - -- - -6 - - - - CO D al' D Cpa D Pal Ser Arg D Pal Leu Arg Pro D Al 10

-a-NH-- -- - - ---6 - - -0 -(-4)D-N-ar-D-Cpa-D-Phe-Ser-Gln-D Pal-Leu-Arg- 9 -a-NH-- -- - - --6 - - -0 -(-4)D-N-ar-D-Cpa-D-Phe-Ser-Gln-D Pal-Leu-Arg- 9

Pro- 0 Pro- 0

D-Ala!-NH D-Ala!-NH

(5 -- -- )D-N- - - -- -- D C - - - pa D Pal Ser G 9 ln D Pal Le (5 -- -- )D-N- - - -- -- D C - - - pa D Pal Ser G 9 ln D Pal Le

?-al' u Arg Pro D Al l ?-al' u Arg Pro D Al l

a NH a NH

(6)Ac D-N- al1 D-C- pa D-P- he S- er G- ln D- - P- al Leu A- -9 -- - rg P ro D Al 1 (6)Ac D-N- al1 D-C- pa D-P- he S- er G- ln D- - P- al Leu A- -9 -- - rg P ro D Al 1

a NH a NH

(7)Ac D NarD Cpa D Pal Ser Gln D Pal Leu Arg P ro D Ala' (7)Ac D NarD Cpa D Pal Ser Gln D Pal Leu Arg P ro D Ala'

(8)NH-NH-- -- -- - - -- - CO D Na (8)NH-NH-- -- -- - - -- - CO D Na

10 rD Cpa D Phe Ser Gln D Pal Leu Arg 9 10 rD Cpa D Phe Ser Gln D Pal Leu Arg 9

Pro D Ala N Pro D Ala N

(9)NH-C0-D-H (9) NH-C0-D-H

-N- - a1'-D- - C-pa-D-Pa - 1-Se - r-G- In-D- -- - - 6- Pa1- - Leu-Arg -Pro-D-Ala10-NH -N- - a1'-D- - C-pa-D-Pa - 1-Se - r-G- In-D- -- - - 6- Pa1- - Leu-Arg -Pro-D-Ala10-NH

(lOD Nal' D Cpa' D Phe Ser Asn' D Pal' Leu' Arg Pro D Al l (lOD Nal' D Cpa' D Phe Ser Asn' D Pal' Leu' Arg Pro D Al l

a NH a NH

(11)D Na1' D Cpa D Pa1 Ser Asn D Pa1 Leu Arg Pro D Al l (11)D Na1' D Cpa D Pa1 Ser Asn D Pa1 Leu Arg Pro D Al l

a NH a NH

(12)Ac-D-Nar-D-Cpa-D-Phe-Ser-Asn-D- 6 (12)Ac-D-Nar-D-Cpa-D-Phe-Ser-Asn-D- 6

Pal-Leu-Arg- 9 -- -- -- - - -- - - - Pro--D--Ala10--NH Pal-Leu-Arg- 9 -- -- -- - - -- - - - Pro--D--Ala10--NH

(13)Ac D-Na-1' D-Cp-a D-Pa-1 Se-r As-n D-Pa-1 Le-u Ar-g Pr-o D-Al-a10 NH- (13)Ac D-Na-1' D-Cp-a D-Pa-1 Se-r As-n D-Pa-1 Le-u Ar-g Pr-o D-Al-a10 NH-

(14)NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Asn-D-Pal-Leu-Arg-Pro-D-A 0(14) NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Asn-D-Pal-Leu-Arg-Pro-D-A 0

la1 NH La1 NH

?- ?-

(15)N-H CO-D-Na1!-D-Cpa -D Pa1-Ser--Asn -D Pa1-Leu-Ar - g-Pro -D Ala' NH (15) N-H CO-D-Na1!-D-Cpa -D Pa1-Ser--Asn -D Pa1-Leu-Ar - g-Pro -D Ala' NH

(16)D NarD C 6 (16)D NarD C 6

pa D Phe Ser Mph D Pal Leu Arg Pro D Alal NH Pa D Phe Ser Mph D Pal Leu Arg Pro D Alal NH

(17)D--Na-r-D--Cp-a-D--Pa-l-Se-r-Mp-h-D--Pa-l-Le-u-Ar-g-Pr-o -D-A-la-l-NH- (17) D--Na-rD--Cp-aD--Pa-l-Se-r-Mp-hD--Pa-l-Le-u-Ar-g-Pr-o-DA-la-l -NH-

(18)Ac-D Na1' D Cpa D Phe-Ser-Mph(18)Ac-D Na1' D Cpa D Phe-Ser-Mph

0 - -- -- -D-Pal-Leu-Arg- Pro-D-Ala1-NH 0 - -- -- -D-Pal-Leu-Arg- Pro-D-Ala1-NH

(19)Ac D-Na-rD-Cp-a D-Pa-l Se-r Mp-h D-Pa-l Le-u Ar-gPr-o D-Al-a10 (19)Ac D-Na-rD-Cp-a D-Pa-l Se-r Mp-h D-Pa-l Le-u Ar-gPr-o D-Al-a10

NH- NH-

(20)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Ar g- 9(20) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mph-D-Pal-Leu-Ar g- 9

Pro-D-Ala10-NH Pro-D-Ala10-NH

(21)NH CO D Na1' D Cpa D Pa1 Ser Mph D Pa1 Leu Ar g Pro D Ala1 NH (21) NH CO D Na1' D Cpa D Pa1 Ser Mph D Pa1 Leu Ar g Pro D Ala1 NH

(22)Ac--D--Na1'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg-- Pro--D--Ala10--NH (22)Ac--D--Na1'--D--Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg-- Pro--D--Ala10 --NH

(23)Ac D Na1' D-Cpa-D-Phe-Ser-Aph-D 6 (23)Ac D Na1' D-Cpa-D-Phe-Ser-Aph-D 6

- -Mop-Leu-Arg 9 -- - Pro-D-Ala10 - -Mop-Leu-Arg 9 -- - Pro-D-Ala10

-NH -NH

(24)Ac D Na a D Phe Ser' Uph D Mop Leu Arg (24)Ac D Na a D Phe Ser' Uph D Mop Leu Arg

0 0

Pro D Ala1 rD CpPro D Ala1 rD Cp

NH NH

(25)Ac-D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu- -- -- -- - - -- - A 8 - rg--P 9(25)Ac-D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu- -- -- -- -- -- -- - A 8 - rg--P 9

ro--D--Ala10--NH ro--D--Ala10--NH

6 6

(26)Ac-D-Nal' D-Cpa'-D-Phe'-Ser'-Phe(NNM)-D-Mop-Leu- A 0 - rg-Pro-D-Ala1-NH (26)Ac-D-Nal' D-Cpa'-D-Phe'-Ser'-Phe(NNM)-D-Mop-Leu- A 0 - rg-Pro-D-Ala1-NH

(27)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-6 (27)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-6

Leu-Arg-Pro--D Ala-10 Leu-Arg-Pro--D Ala-10

NH NH

(28)Ac-D-Nar-D-Cpa-D-Phe-Ser'-Aph(A 6 (28)Ac-D-Nar-D-Cpa-D-Phe-Ser'-Aph (A 6

c) -D M-op -Leu -A rg -Pro -D-Ala10-NH c) -D M-op -Leu -A rg -Pro -D-Ala10-NH

(29)Ac D Nal1 D Cpa D Phe Ser Aph(DMe) 6 (29)Ac D Nal1 D Cpa D Phe Ser Aph(DMe) 6

D Mop Leu Arg Pro D Ala10 D Mop Leu Arg Pro D Ala10

NH NH

(30)D-Nar-D-Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg--Pro9 - -D--Alal - -- --NH (30) D-Nar-D-Cpa--D--Phe--Ser--Phe--D--Mop--Leu--Arg--Pro9 - -D--Alal - -- --NH

(31) 9 D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg-Pro-D-Alal-NH (31) 9 D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg-Pro-D-Alal-NH

(32)D-Nal'-D-Cpa-D-Phe-Ser-Uph D Mo-p-Leu-Arg-Pro -D Al-al-NH - (32) D-Nal'-D-Cpa-D-Phe-Ser-Uph D Mo-p-Leu-Arg-Pro-D Al-al-NH -

(33)D-Nal' D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu-Arg -Pro-D-Ala10 - -NH (33) D-Nal' D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu-Arg-Pro-D-Ala10 - -NH

(34)D Nal1 D Cpa D Phe Ser Phe(NOM) D Mop Leu Arg Pro D Ala10 (34)D Nal1 D Cpa D Phe Ser Phe(NOM) D Mop Leu Arg Pro D Ala10

NH NH

(35)D--Nal1--D--Cpa--D--Phe--Ser--Aph(Ac)--D-M-o 6 (35) D--Nal1--D--Cpa--D--Phe--Ser--Aph(Ac)--D-M-o 6

p--Leu--Arg --P 9 p--Leu--Arg --P 9

ro--D--Ala!0--NH ro--D--Ala!0--NH

(36)D Na - er Ap (36)D Na - er Ap

-Pro -D-A 10rD Cpa--D Phe--S -h(D-Me) -D-Mop-Leu-Arg 9 - la -NH -Pro -D-A 10rD Cpa--D Phe--S -h(D-Me) -D-Mop-Leu-Arg 9 - la -NH

(37)NH CO D NarD Cpa D Phe Ser Phe D Mop Leu Ar 9 (37) NH CO D NarD Cpa D Phe Ser Phe D Mop Leu Ar 9

g Pro D Ala10g Pro D Ala10

NH NH

(38)NH CO-D-Nal'-D-Cpa'-D-Phe'-Ser'-Aph'-D-Mop'-Leu'-Ar 9 -- -- -- - - -- - - g--Pro--D--Ala10--NH(38) NH CO-D-Nal'-D-Cpa'-D-Phe'-Ser'-Aph'-D-Mop'-Leu'-Ar 9 -- -- -- - - -- - - g--Pro--D--Ala10--NH

6 6

(39)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Uph D Mo-p-Leu-Ar g- 9 (39) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Uph D Mo-p-Leu-Ar g- 9

Pro-D Al-a1-0 Pro-D Al-a1-0

NH - NH -

(40)NH CO-D-Na(40) NH CO-D-Na

1r-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu-Arg-Pro-D-A 0 1r-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Leu-Arg-Pro-D-A 0

la-NH la-NH

(41)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Le u-Arg- 9 (41) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Le u-Arg- 9

Pro-D-Ala1-NH Pro-D-Ala1-NH

(42)NH CO D Nal' D Cpa D Phe Ser Phe(NOM) D Mop Le u Arg Pro D Ala10 (42) NH CO D Nal' D Cpa D Phe Ser Phe (NOM) D Mop Le u Arg Pro D Ala10

NH NH

(43)NH CO--D--Nar--D--Cpa--D--Phe--Ser'--Aph(Ac)--D-M-op--Leu --Arg--Pro--D-A-la1--NH (43) NH CO--D--Nar--D--Cpa--D--Phe--Ser'--Aph(Ac)--DM-op--Leu --Arg--Pro--DA -la1--NH

(44)NH C-O-D Na -D Cp-a-D Ph-e Se-r Ap-h(-DMe)-D Mo-p Le- u Ar-g-Pro -AlaI-l' (44) NH C-O-D Na -D Cp-a-D Ph-e Se-r Ap-h(-DMe)-D Mo-p Le- u Ar-g-Pro -AlaI-l'

0 0

D NH D NH

(45)NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg -Pro-D-AlaI0-NH (45) NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-Arg-Pro-D-AlaI0-NH

(46)NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg - 9 (46) NTA-D-Nal1-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-Arg - 9

Pro-D-Ala10-NH Pro-D-Ala10-NH

(47)NTA D NarD Cpa D Phe Ser Uph D Mop Leu Arg Pro D Ala1 NH (47)NTA D NarD Cpa D Phe Ser Uph D Mop Leu Arg Pro D Ala1 NH

(48)NTA--D--Nal1--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Leu - -Arg--Pro--D--Ala1--NH (48) NTA--D--Nal1--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Leu--Arg--Pro--D- -Ala1--NH

(49)NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Leu-Arg-Pro-D-Ala1-NH (49) NTA-D-Nar-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Leu-Arg-Pro-D-Ala1-NH

(50)NTA D Na1' D Cpa' D Phe' Ser' Phe(NOM) D Mop Leu A 9 (50)NTA D Na1' D Cpa' D Phe' Ser' Phe(NOM) D Mop Leu A 9

rg Pro D Ala10 Rg Pro D Ala10

NH NH

(51)NTA-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph(Ac)-D-Mop-Leu- -- -- -- - - -- - - Arg--Pro--D--A 0(51)NTA-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph(Ac)-D-Mop-Leu- -- -- -- - -- -- - - Arg--Pro--D--A 0

la1--NH la1--NH

(52)NTA-D-Nar-D-Cpa-D-Phe-Ser-Aph(-DM-e) D-Mop-Leu 9 (52) NTA-D-Nar-D-Cpa-D-Phe-Ser-Aph(-DM-e) D-Mop-Leu 9

-Arg-P-ro D-Ala10-Arg-P-ro D-Ala10

NH NH

6 6

(53)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-A 8 rg -Pro-D-Ala10-NH (53)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe-D-Mop-Leu-A 8 rg -Pro-D-Ala10-NH

6 6

(54)NDN-D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-A 8 rg -Pro-D-Ala10-NH (54)NDN-D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Mop-Leu-A 8 rg -Pro-D-Ala10-NH

(55)NDN D NarD Cpa D Phe Ser Uph D M 6 (55)NDN D NarD Cpa D Phe Ser Uph D M 6

op Leu Arg Pro D Ala10 NH Op Leu Arg Pro D Ala10 NH

(56)NDN--D--Na1'--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Leu - -Arg--Pro--D--Ala10--NH (56)NDN--D--Na1'--D--Cpa--D--Phe--Ser--Phe(NAM)--D--Mop--Leu - -Arg--Pro--D --Ala10--NH

( 6 57)NDN-D-Nal'-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Leu-Arg-Pro-D-Ala10 ( 6 57)NDN-D-Nal'-D-Cpa-D-Phe-Ser-Phe(NNM)-D-Mop-Leu-Arg-Pro-D-Ala10

-NH -NH

(58)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-Leu- Arg-Pro-9 (58)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe(NOM)--D Mop-Leu- Arg-Pro-9

-D Ala-10 -D Ala-10

NH NH

(59)NDN-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph(Ac) -D M-op -Leu - Arg -Pro -D-Ala10-NH (59)NDN-D-Na1'-D-Cpa'-D-Phe'-Ser'-Aph(Ac) -D M-op -Leu - Arg -Pro -D-Ala10-NH

(60)NDN D NarD Cpa D Phe Ser Aph(DMe) D Mop Leu Arg Pro D Ala10 (60)NDN D NarD Cpa D Phe Ser Aph(DMe) D Mop Leu Arg Pro D Ala10

NH NH

(61)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe6 (61)Ac--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe6

--Leu--Arg-- Pro--D--Ala10--NH --Leu--Arg-- Pro--D--Ala10--NH

(62)A 6 (62) A 6

c-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg- Pro-D-Ala10 c-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg- Pro-D-Ala10

-NH -NH

(63)Ac D Na1! D Cpa D Phe Ser Mop D Uph Leu ArgPro D Ala10 (63)Ac D Na1! D Cpa D Phe Ser Mop D Uph Leu ArgPro D Ala10

NH NH

(64)Ac-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu- 3 "8 -- -- -- - - -- - - Arg--Pro--D--Ala10(64)Ac-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu- 3 "8 -- -- -- - -- -- - - Arg--Pro--D--Ala10

--NH --NH

(65)Ac-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6 (65)Ac-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6

-Leu- A 9 -Leu- A 9

rg-Pro-D-Ala10 rg-Pro-D-Ala10

-NH -NH

(66)Ac-D-Nal'-D-Cpa-D-Phe-Ser'-Mop-D-Phe(NOM)6 (66)Ac-D-Nal'-D-Cpa-D-Phe-Ser'-Mop-D-Phe(NOM)6

-Leu- s Arg-Pro--D Ala-10 -Leu- s Arg-Pro--D Ala-10

NH NH

(67)Ac-D-Na1-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac) A r - 9 -Leu - g Pro -D-Ala10 (67)Ac-D-Na1-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac) A r - 9 -Leu - g Pro -D-Ala10

-NH -NH

(68)Ac D NarD Cpa D Phe Ser' Mop D Aph(DMe) Leu Arg Pro D Ala10 (68)Ac D NarD Cpa D Phe Ser' Mop D Aph (DMe) Leu Arg Pro D Ala10

NH NH

0 (69)D--Nal'--D--Cpa--D--Phe--Ser--Mop--D--Phe6--Leu--Arg--Pro9 - -D--Alal--NH 0 (69)D--Nal'--D--Cpa--D--Phe--Ser--Mop--D--Phe6--Leu--Arg--Pro9 - -D--Alal-- NH

(70)D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg-Pro -D-Alal-NH (70) D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Arg-Pro-D-Alal-NH

(71)D-Nar 9 (71)D-Nar 9

-D-Cpa-D-Phe-Ser-Mop-D-Uph Leu-Arg-Pro -D Al-al-NH - -D-Cpa-D-Phe-Ser-Mop-D-Uph Leu-Arg-Pro -D Al-al-NH -

(72)D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg -Pro-D-Ala10-NH (72) D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg-Pro-D-Ala10-NH

(73)D Nal' D Cpa D Phe Ser Mop D Phe(NNM)6 (73)D Nal' D Cpa D Phe Ser Mop D Phe(NNM)6

Leu Arg Pro D Ala10 Leu Arg Pro D Ala10

NH NH

(74)D--Nar-D-Cpa-D-Phe--Ser--Mop--D--Phe(NOM)6 (74) D--Nar-D-Cpa-D-Phe--Ser--Mop--D--Phe(NOM)6

--Leu--Arg --Pro--D--Ala1 -- -- --NH --Leu--Arg --Pro--D--Ala1 -- -- --NH

(75)D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac) -Leu -Arg -Pro-D-Ala10 (75) D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac) -Leu -Arg -Pro-D-Ala10

-NH -NH

(76)D Nal' D Cpa' D Phe' Ser'Mop'D Aph(DMe) Leu Arg Pro D Ala10 (76)D Nal' D Cpa' D Phe' Ser'Mop'D Aph(DMe) Leu Arg Pro D Ala10

NH NH

(77)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Ar -- -- -- - - -- - - g--Pro--D--Ala10--NH (77) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Ar -- -- -- - -- -- - - g--Pro--D--Ala10--NH

(78)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Ar g- 9 (78) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-Ar g- 9

Pro-D-Ala10 Pro-D-Ala10

?-NH ?-NH

(79)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph Leu-Arg- 9 (79) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph Leu-Arg- 9

Pro-D Al-a'-NH - Pro-D Al-a'-NH -

(80)NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)6-Le u-Arg-Pro-D-Ala10-NH (80) NH CO-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)6-Le u-Arg-Pro-D-Ala10-NH

(81)NH CO D Na Cpa D Phe Ser Mop D Phe(NNM) Le (81) NH CO D Na Cpa D Phe Ser Mop D Phe(NNM) Le

9 rD 9 rD

u Arg Pro D Ala10u Arg Pro D Ala10

NH NH

(82) 6 NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)--Le u--Arg--Pro---D-Ala-10-NH (82) 6 NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(NOM)--Le u--Arg--Pro- --D-Ala-10-NH

(83)NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)6 (83) NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)6

-Leu -Arg -Pro -D-Ala10-NH -Leu -Arg -Pro -D-Ala10-NH

(84)NH C-O-D Na D Cp-a-D Ph-e Se-r' Mo (84) NH C-O-D Na D Cp-a-D Ph-e Se-r' Mo

-- - 0-r- -p-D Ap-h(DMe-) Le -u A 9 -- - 0-r- -p-D Ap-h(DMe-) Le -u A 9

rg Pro D Ala1 NH Rg Pro D Ala1 NH

(85)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Arg -Pro-D-Ala10-NH (85)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Arg-Pro-D-Ala10-NH

(86)NTA D NarD Cpa D Phe Ser' Mop D Aph Leu Arg 9 (86)NTA D NarD Cpa D Phe Ser' Mop D Aph Leu Arg 9

Pro D Ala10 Pro D Ala10

NH NH

(87)NTA--D--Nar--D--Cpa--D--Phe--Ser'--Mop--D--Uph-Leu--Arg - -Pro--D-Al-a1-0-NH - (87)NTA--D--Nar--D--Cpa--D--Phe--Ser'--Mop--D--Uph-Leu--Arg--Pro--D-Al-a1 -0-NH -

(88)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg- 9(88) NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NAM)-Leu-Arg- 9

Pro-D-Ala10-NH Pro-D-Ala10-NH

(89)NTA D NarD Cpa D Phe Ser Mop D Phe(NNM)6 (89)NTA D NarD Cpa D Phe Ser Mop D Phe(NNM)6

Leu Arg Pro D Ala10 Leu Arg Pro D Ala10

NH NH

(90)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Leu -- -- -- - - -- - - -Arg-8-Pro--D--Ala-10-NH (90)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Leu -- -- -- - - -- - - -Arg-8-Pro--D--Ala-10-NH

(91)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)6 (91)NTA-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph(Ac)6

-Leu- Arg -Pro -D-Ala10-NH -Leu- Arg -Pro -D-Ala10-NH

(92)NTA-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(-DMe)-Leu -Arg-P-ro D-Ala10 NH (92)NTA-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Aph(-DMe)-Leu-Arg-P-ro D-Ala10 NH

8 8

(93)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Arg -Pro-D-Ala10-NH (93)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe-Leu-Arg-Pro-D-Ala10-NH

(94)NDN D Nal1 D Cpa D Phe Ser Mop D Aph Leu Arg Pro D Ala10 (94)NDN D Nal1 D Cpa D Phe Ser Mop D Aph Leu Arg Pro D Ala10

NH NH

(95)NDN--D--Nar--D--Cpa--D--Phe--Ser'--Mop--D--Uph-Leu--Arg - -Pro--D-Al-a!-0-NH - (95)NDN--D--Nar--D--Cpa--D--Phe--Ser'--Mop--D--Uph-Leu--Arg--Pro--D-Al-a !-0-NH -

(96)NDN-D-Nal1-D-Cpa-D-Phe-Ser'-Mop-D-Phe(NAM)-Leu-Arg-Pro-D-Ala1-NH (96)NDN-D-Nal1-D-Cpa-D-Phe-Ser'-Mop-D-Phe(NAM)-Leu-Arg-Pro-D-Ala1-NH

(97)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Leu -Arg-Pro-D-Ala1-NH (97)NDN-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)-Leu-Arg-Pro-D-Ala1-NH

(98)NDN-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)6 (98)NDN-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)6

-Leu- Arg-Pro--D Ala-10 -Leu- Arg-Pro--D Ala-10

NH NH

(99)NDN D NarD Cpa D Phe Ser Mop D Aph(Ac)6 (99)NDN D NarD Cpa D Phe Ser Mop D Aph(Ac)6

Leu Arg Pro D Ala10 Leu Arg Pro D Ala10

NH NH

(100)ND-N--D-Nal-'--D-Cpa'--D-Phe-'-Ser-'-Mop-'--D-Aph(DMe)-6-Le - u-Ar-g--Pro--D-Ala10-NH (100) ND-N--D-Nal-'--D-Cpa'--D-Phe-'-Ser-'-Mop-'--D-Aph(DMe)-6-Le-u-Ar -g--Pro--D-Ala10-NH

(lODAc-D-Nar-D-Cpa-D-Phe'-Ser'-Leu'-D-Mop-Leu'-Arg-Pro-D-Ala10 (lODAc-D-Nar-D-Cpa-D-Phe'-Ser'-Leu'-D-Mop-Leu'-Arg-Pro-D-Ala10

-NH -NH

(102)Ac D Nal' D Cpa D Phe Ser Tyr D Mop Leu Arg Pro D Ala10 (102)Ac D Nal' D Cpa D Phe Ser Tyr D Mop Leu Arg Pro D Ala10

NH NH

(103)Ac-D-Nar-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-Arg -- -- -- - - -- - - - 9 (103)Ac-D-Nar-D-Cpa-D-Phe-Ser-Lys-D-Mop-Leu-Arg -- -- -- - - -- - - - 9

-Pro--D--Ala10--NH -Pro--D--Ala10--NH

(104)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Glu-D-Mop-Leu-Arg-Pro-D-Ala1-NH (104)Ac-D-Nal1-D-Cpa-D-Phe-Ser-Glu-D-Mop-Leu-Arg-Pro-D-Ala1-NH

(105)Ac-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop-Leu-Arg -Pro-D-Ala1-NH (105)Ac-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop-Leu-Arg-Pro-D-Ala1-NH

(106)A-c D N-al-' D C-pa-D P-he S-er A-rg-D M-op L-eu A 8 (106) A-c D N-al-' D C-pa-D P-he S-er A-rg-D M-op L-eu A 8

-rg P-ro-9 D A-la10 -rg P-ro-9 D A-la10

NH NH

(107)D NarD Cpa D Phe Ser Leu D Mop Leu Arg Pr o D Ala10 NH (107)D NarD Cpa D Phe Ser Leu D Mop Leu Arg Pr o D Ala10 NH

(108)D--Nar--D--Cpa--D--Phe--Ser--Tyr--D--Mop--Leu--Arg--Pr o--D--Ala10--NH (108) D--Nar--D--Cpa--D--Phe--Ser--Tyr--D--Mop--Leu--Arg--Pr o--D--Ala10--NH

(109)D NarD Cpa D Phe Ser (109)D NarD Cpa D Phe Ser

0 - -- -- - -Lys-D-Mop-Leu-Arg-Pr o-D-Ala1-NH 0 - -- -- - -Lys-D-Mop-Leu-Arg-Pr o-D-Ala1-NH

(110)D-Nar-D-Cpa-D-Phe-Ser-G1u-D-Mop-Leu'-Arg-Pro-D-Ala1-NH (110)D-Nar-D-Cpa-D-Phe-Ser-G1u-D-Mop-Leu'-Arg-Pro-D-Ala1-NH

( 8 111)D-Na1!-D-Cpa-D-Phe-Ser-G 6 ( 8 111)D-Na1!-D-Cpa-D-Phe-Ser-G 6

In-D-Mop-Leu-Arg-Pr o-D-Ala1-NH In-D-Mop-Leu-Arg-Pr o-D-Ala1-NH

(112)D Nal' D Cpa' D Phe' Ser' Arg' D Mop'Leu' Arg' Pr 9 (112)D Nal' D Cpa' D Phe' Ser' Arg' D Mop'Leu' Arg' Pr 9

o D Ala10 NHo D Ala10 NH

(113)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Leu--D--Mop--Leu--A rg--Pro--D--Ala10--NH (113) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Leu--D--Mop--Leu--A rg--Pro--D-- Ala10--NH

(114)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mop-Leu-A rg-Pro-D-Ala1-NH (114) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Tyr-D-Mop-Leu-A rg-Pro-D-Ala1-NH

(115)NH CO D Nal' D Cpa D Phe Ser Lys D 6 (115)NH CO D Nal' D Cpa D Phe Ser Lys D 6

Mop Leu Arg Pro D Ala1 NH Mop Leu Arg Pro D Ala1 NH

(116)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Glu-D-Mop6-Leu-A - -- -- - - -- - - rg--Pro--D--Ala1-0--NH (116) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Glu-D-Mop6-Leu-A - -- -- - - -- - - rg--Pro--D--Ala1-0--NH

(117)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop-Leu-A 9 (117) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop-Leu-A 9

rg-P -D-A 1rg-P -D-A 1

ro la-NH Ro la-NH

6 6

(118)N-H CO-D-Na1'-D-Cpa -D Phe-Ser Arg-D-Mop-Leu-Arg-Pro-9-D Ala-10 (118) N-H CO-D-Na1'-D-Cpa -D Phe-Ser Arg-D-Mop-Leu-Arg-Pro-9-D Ala-10

NH NH

(119)D N-a1-' D C-pa-'D P-he-' Ser-' Phe-(NNM) D Mo-p-Leu-Ar g - 9 (119)D N-a1-' D C-pa-'D P-he-' Ser-' Phe-(NNM) D Mo-p-Leu-Ar g - 9

Pro -D Ala-10-NH - Pro -D Ala-10-NH -

(120)NTA D Na1' D Cpa' D Phe'Ser' Phe(COOH) D Mop L(120)NTA D Na1' D Cpa' D Phe'Ser' Phe(COOH) D Mop L

9 9

eu A 8Eu A 8

rg Pro D Ala10 Rg Pro D Ala10

NH NH

(121)NTA--D--Nar--D--Cpa--D--Phe--Ser--Phe(-CA-M)-D-Mop--Le u--Arg--Pro--D--Ala10--NH (121) NTA--D--Nar--D--Cpa--D--Phe--Ser--Phe(-CA-M)-D-Mop--Le u--Arg--Pro-- D--Ala10--NH

( ] ( ]

122)NTA-D-Na1-D-Cpa-D-Phe-Ser-Mop-D-Phe(COOH)-L eu-Arg-Pro--D Ala-10 122) NTA-D-Na1-D-Cpa-D-Phe-Ser-Mop-D-Phe(COOH)-L eu-Arg-Pro--D Ala-10

NH NH

(123)NTA-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop' D Phe-(C-AM)6 (123)NTA-D-Na1'-D-Cpa'-D-Phe'-Ser'-Mop' D Phe-(C-AM)6

-Leu -Arg -Pro -D-Ala1 -NH -Leu -Arg -Pro -D-Ala1 -NH

(124)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-L eu-Arg-Pro--D Ala-10 (124)NDN-D-Nar-D-Cpa-D-Phe-Ser-Phe(COOH)--D Mop-L eu-Arg-Pro--D Ala-10

NH NH

(125)NDN D Nal1 D Cpa D Phe Ser Phe(CAM) D Mop Le u A 8 (125)NDN D Nal1 D Cpa D Phe Ser Phe(CAM) D Mop Le u A 8

rg Pro D AlaI0 Rg Pro D AlaI0

NH NH

(126)NDN--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(COOH)--L eu--Arg--Pro-9--D-Ala-10-NH (126)NDN--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Phe(COOH)--L eu--Arg--Pro-9- -D-Ala-10-NH

(127)NDN (127)NDN

9 -D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10 9 -D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-Le u-Arg-Pro-D-Ala10

-NH -NH

(128)CAM D Nal1 D Cpa D Phe Ser Mop D Phe(NAM) Le (128)CAM D Nal1 D Cpa D Phe Ser Mop D Phe(NAM) Le

9 9

u Arg Pro D Ala10 NH u Arg Pro D Ala10 NH

(129)CAM-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6-Le 9 -- -- -- - - -- - U--Arg--Pro--D--Ala10--NH (129) CAM-D-Nal1-D-Cpa-D-Phe-Ser-Mop-D-Phe(NNM)6-Le 9 -- -- -- - - -- - U--Arg--Pro--D--Ala10--NH

(130)CAM-D-Na1! D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Le u-Arg-Pro-D-Ala10- -NH (130) CAM-D-Na1! D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Le u-Arg-Pro-D-Ala10- -NH

(131)CAM-D-Nal' (131) CAM-D-Nal'

Arg -Pro -D-A I0-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM) -Le s u - la -NH Arg -Pro -D-A I0-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM) -Le s u - la -NH

NH NH

(133)CEC D Nal1 D Cpa D Phe Ser Mop D Phe(NAM)6 (133)CEC D Nal1 D Cpa D Phe Ser Mop D Phe(NAM)6

Le u Arg Pro D Ala10 Le u Arg Pro D Ala10

NH NH

0 (134)CEC--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Phe(NNM)6--Le u--A 90 (134)CEC--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Phe(NNM)6--Le u--A 9

rg--Pro--D--Ala10--NH rg--Pro--D--Ala10--NH

(135)CEC (135) CEC

8 -D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Le u-Arg-Pro-D-Ala10-NH 8-D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Phe(NOM)-Le u-Arg-Pro-D-Ala10-NH

(136)CEC-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Phe(CAM) -Les u -Arg - 9 (136)CEC-D-Nal'-D-Cpa'-D-Phe'-Ser'-Mop'-D-Phe(CAM) -Les u -Arg - 9

Pro -D-Ala10-NH Pro -D-Ala10-NH

(137)CEC-D-Nal' D Cpa' D Phe' Ser' Mop' D Ph-e(-COOH)-L -A 0-- -- - - eu rg-Pro--D Ala-1 NH (137)CEC-D-Nal' D Cpa' D Phe' Ser' Mop' D Ph-e(-COOH)-L -A 0-- -- - - eu rg-Pro--D Ala-1 NH

(138)CAM D Na1! D Cpa D Phe Ser' Phe(NAM) D Mop Le u Arg Pro D Ala10 (138)CAM D Na1! D Cpa D Phe Ser' Phe(NAM) D Mop Le u Arg Pro D Ala10

NH NH

(139)CAM--D--Nar--D--Cpa--D--Phe--Ser--Phe(NNM)--D--Mo 6 p--Le u--Arg--Pro--D--Ala10--NH (139)CAM--D--Nar--D--Cpa--D--Phe--Ser--Phe(NNM)--D--Mo 6 p--Le u--Arg--Pro- -D--Ala10--NH

(140)CAM-D-Na1'-D-Cpa'-D-Phe'-Ser'-Phe(NOM)-D-Mop (140) CAM-D-Na1'-D-Cpa'-D-Phe'-Ser'-Phe(NOM)-D-Mop

9 -Le u-Arg-Pro-D-Ala1-NH 9 -Le u-Arg-Pro-D-Ala1-NH

(141)CAM D NarD Cpa D Phe Ser Phe(CAM) D Mop Le u Arg Pro D Ala10 (141) CAM D NarD Cpa D Phe Ser Phe (CAM) D Mop Le u Arg Pro D Ala10

NH NH

(142)CAM-D-Nal'-D-Cpa'-D-Phe'-Ser'-Phe(COOH)-D-Mop-L -- -- -- - - -- - eu--Arg--Pro-9--D-Ala-10-NH (142) CAM-D-Nal'-D-Cpa'-D-Phe'-Ser'-Phe(COOH)-D-Mop-L -- -- -- - -- -- - eu--Arg--Pro-9--D-Ala-10-NH

(143)CEC-D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Le -A 9 (143) CEC-D-Nar-D-Cpa-D-Phe-Ser-Phe(NAM)-D-Mop-Le-A 9

u rg-Pro-D-Ala10-NH u rg-Pro-D-Ala10-NH

(144)CEC-D-Nal1-D-Cpa-D-Phe-Ser-Phe(NNM)-D (144) CEC-D-Nal1-D-Cpa-D-Phe-Ser-Phe(NNM)-D

9 -Mop-Leu-Arg-Pro-D-Ala10-NH 9 -Mop-Leu-Arg-Pro-D-Ala10-NH

(145)CEC-D-NarD-Cpa-D-Phe-Ser-Phe(NOM)-D-Mop-Le u-Arg-Pro-D-Ala10- -NH (145) CEC-D-NarD-Cpa-D-Phe-Ser-Phe(NOM)-D-Mop-Le u-Arg-Pro-D-Ala10- -NH

(146)CEC D NarD Cpa D Phe Ser Phe(CAM) D M 6 op Le u Arg Pro D Ala10 (146) CEC D NarD Cpa D Phe Ser Phe (CAM) D M 6 op Le u Arg Pro D Ala10

NH NH

(147)CEC-D--N-ar-D--C-pa-D--P-he-S-er-P-he(C-OO-H)-D--Mop--L eu--Arg--P-ro-D--Ala10-NH (147) CEC-D--N-ar-D--C-pa-D--P-he-S-er-P-he(C-OO-H)-D--Mop--L eu- -Arg--P-ro-D--Ala10-NH

(148)NH CO D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Aph-Leu-A 9 - rg-Pro-D-Ala10 (148) NH CO D-Nar-D-Cpa-D-Phe-Ser-Aph-D-Aph-Leu-A 9 - rg-Pro-D-Ala10

-NH -NH

(149)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-A 6 (149) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-A 6

ph Leu-Arg-Pro-D-Ala10 Ph Leu-Arg-Pro-D-Ala10

-NH -NH

(150)NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Uph'-D-Aph-Leu'-A rg-Pro-D-Ala1-NH (150) NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Uph'-D-Aph-Leu'-A rg-Pro-D-Ala1-NH

( 6 (6

151)NH CO D NarD Cpa D Phe Ser Aph D Uph Leu A rg Pro D Ala10 151) NH CO D NarD Cpa D Phe Ser Aph D Uph Leu A rg Pro D Ala10

NH NH

(152)NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Gln--D--Uph--Leu--A rg--Pro--D--Ala10--NH (152) NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Gln--D--Uph--Leu--A rg--Pro--D-- Ala10--NH

(153)NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Uph' D U-ph-'Leu-' A rg-Pro-D A-la-10 (153) NH CO-D-Na1'-D-Cpa'-D-Phe'-Ser'-Uph' D U-ph-'Leu-' A rg-Pro-D A-la-10

NH- NH-

(154)NH CO D Na pa D Phe Se D Uph Le(154) NH CO D Na pa D Phe Se D Uph Le

0rD C r Aph(Ac) 6 u Arg P 9 0rD C r Aph(Ac) 6 u Arg P 9

ro D Ala1 NH Ro D Ala1 NH

(155)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Aph(Ac )-Leu-Arg-P 9(155) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Aph(Ac )-Leu-Arg-P 9

ro-D-Ala10-NH ro-D-Ala10-NH

(156)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Aph(Ac)-Le (156) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Aph(Ac)-Le

9 9

u-Arg-Pro-D-Ala10-NH u-Arg-Pro-D-Ala10-NH

(157)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Uph-D-Aph(Ac)-Le (157) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Uph-D-Aph(Ac)-Le

9 9

u-Arg-Pro-D-Ala10-NH u-Arg-Pro-D-Ala10-NH

(158)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-C it--Pro--D-A-la-10-NH- (159)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(-Ac)--Le u Cit Pro D Ala10 (158) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-C it--Pro--DA-la-10-NH- (159)NH CO-- D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(-Ac)--Le u Cit Pro D Ala10

NH NH

6 6

(160)NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu I (160)NH CO D Nal' D Cpa D Phe Ser Mop D Aph Leu I

Iys-Pro-D-Ala10-NH Iys-Pro-D-Ala10-NH

(161)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-I orn-Pro-D-Ala1-NH (161) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-I orn-Pro-D-Ala1-NH

(162)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-A rg-Pro-D-Ala10-NH (162) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-A rg-Pro-D-Ala10-NH

(163)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Pro-D-M 6 (163) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Pro-D-M 6

op-Leu-A rg-Pro-D-Ala10-NH op-Leu-A rg-Pro-D-Ala10-NH

(164)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-G In-Pro-D-Ala10-NH (164) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-G In-Pro-D-Ala10-NH

(165)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph6-Leu-L ys(Bzl)-Pro-D-Ala10-NH (165) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph6-Leu-L ys(Bzl)-Pro-D-Ala10-NH

(166)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-A 6 (166) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-A 6

ph-Leu-A sp-Pro-D-Ala10-NH ph-Leu-A sp-Pro-D-Ala10-NH

(167)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Asn-Leu-A 9 (167) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Asn-Leu-A 9

rg-Pro-D-Ala10-NH rg-Pro-D-Ala10-NH

(168)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Gl 6 (168) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Gl 6

u-Leu-A -- -- -- - - -- - - rg--Pro--D--Ala10--NHu-Leu-A -- -- -- - - -- - - rg--Pro--D--Ala10--NH

6 6

(169)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-G Iu-Pro-D-Ala1-NH (169) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Aph-Leu-G Iu-Pro-D-Ala1-NH

(170)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph Leu-Asn-Pro-D A-la-10 (170) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph Leu-Asn-Pro-D A-la-10

NH NH

?- ?-

(171)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Amp(-Ac) -Le u -Arg -Pr-o D A-la' NH(171) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop-D-Amp(-Ac) -Le u -Arg -Pr-o D A-la' NH

6 6

(172)NH CO D NarD Cpa D Phe Ser Mop D Amp Leu A rg Pro D Ala10 (172) NH CO D NarD Cpa D Phe Ser Mop D Amp Leu A rg Pro D Ala10

NH NH

(173)NH CO--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Mop'-Leu--! Lys--Pro--D-Al-a1-0-NH - (173) NH CO--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Mop'-Leu--! Lys--Pro --D-Al-a1-0-NH -

(174)NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-L eu-Ily-s Pr-o-D Ala-10(174) NH CO-D-Na1'-D-Cpa-D-Phe-Ser-Mop-D-Phe(CAM)-L eu-Ily-s Pr-o-D Ala-10

NH NH

(175)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aarp(-Ac) -Leu -Glu -Pr-o D A-la1 NH (175) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aarp(-Ac) -Leu -Glu -Pr-o D A-la1 NH

(176)NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop D M 6 (176) NH CO-D-Nal'-D-Cpa-D-Phe-Ser-Mop D M 6

-op-Leu-G Iu P-ro D-Ala-10-NH - -op-Leu-G Iu P-ro D-Ala-10-NH -

(177)NH CO D NarD Cpa D Phe Ser Aph(Ac) D M 6 op (A c) Arg Pro D Ala10 (177) NH CO D NarD Cpa D Phe Ser Aph(Ac) D M 6 op (A c) Arg Pro D Ala10

c NHc NH

(178)NH CO--D--Na1!--D--Cpa--D--Phe--S 6 er--Aph(-Ac-)-D-Mop--(A cc)--Arg--P 9 (178) NH CO--D--Na1!--D--Cpa--D--Phe--S 6 er--Aph(-Ac-)-D-Mop--(A cc)--Arg --P 9

ro--D--Ala1--NH ro--D--Ala1--NH

(179)NH CO D (179) NH CO D

8 --Na1'-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Ac)-(A cc)-Arg-Pro-D-Ala1-NH 8 --Na1'-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Ac)-(A cc)-Arg-Pro-D-Ala1-NH

(180)NH CO D Nal' D Cpa D Phe Ser' Mop D Aph(Ac) (Acc) Arg Pro D Ala1 NH (180)NH CO D Nal' D Cpa D Phe Ser' Mop D Aph(Ac) (Acc) Arg Pro D Ala1 NH

(181)NTA-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-Arg --Pro--D--Ala10--NH (181)NTA-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Pro-Leu-Arg --Pro--D--Ala10--NH

(182)NTA (182) NTA

0-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop Leu-Arg-Pro-D A-la-1 NH- 0-D-Nar-D-Cpa-D-Phe-Ser-Gln-D-Mop Leu-Arg-Pro-D A-la-1 NH-

U83)NTA-D-Nar-D-Cpa-D-Phe-Ser-Gln D A-ph-(Ac)-Leu Ar-g Pr-o D-Al-a1 NH-U83)NTA-D-Nar-D-Cpa-D-Phe-Ser-Gln D A-ph-(Ac)-Leu Ar-g Pr-o D-Al-a1 NH-

(184)NTA-D-Nar-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Mop-(Ac c )-Arg-Pro-D-Ala10-NH (184) NTA-D-Nar-D-Cpa-D-Phe-Ser-Aph(Ac)-D-Mop-(Ac c )-Arg-Pro-D-Ala10-NH

(185)NTA D NarD Cpa D Phe Ser Aph(Ac) D Mop (Ac 6 (185) NTA D NarD Cpa D Phe Ser Aph(Ac) D Mop (Ac 6

c) Arg Pro D Ala10c) Arg Pro D Ala10

NH NH

(186)NTA--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Aph(Ac)--(Ac (186) NTA--D--Na1'--D--Cpa'--D--Phe'--Ser'--Mop'--D--Aph(Ac)--(Ac

9 9

c)--Arg--Pro--D--Ala10--NH c)--Arg--Pro--D--Ala10--NH

(187)NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(-Ac) -(Ac c-) A-rg- 9 (187) NTA-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(-Ac) -(Ac c-) A-rg- 9

Pro-D AlaI0 Pro-D AlaI0

NH NH

(188)NTA-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-A 6 (188) NTA-D-Na1!-D-Cpa-D-Phe-Ser-Mop-D-A 6

sn-Leu-Arg -Pro-D-Ala10-NH sn-Leu-Arg -Pro-D-Ala10-NH

(189)NTA rg - 9 (189)NTA rg - 9

Pro-D-Ala1-D-Na1'-D-Cpa-D-Phe-Ser'-Mop-D-Glu-Leu-A Pro-D-Ala1-D-Na1'-D-Cpa-D-Phe-Ser'-Mop-D-Glu-Leu-A

-NH -NH

(190)NTA D Nal' D Cpa' D Phe'Ser' Aph' D Mop' Leu' Arg 9 (190)NTA D Nal' D Cpa' D Phe'Ser' Aph' D Mop' Leu' Arg 9

Pro D Ala10 Pro D Ala10

NH NH

(191)NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Aph(Enanth yl-)6-Le-u-Ar-g-Pr-9 (191) NH CO--D--Nal1--D--Cpa--D--Phe--Ser--Mop--D--Aph(Enanth yl-)6-Le-u-Ar-g- Pr-9

o--D-Ala-10-NH o--D-Ala-10-NH

(192)NH CO-D-Nal1-D -D-Phe-Ser-Mop-D Aph(Lauryl ) A 9 - L-eu -rg P-ro D-A- 0 (192) NH CO-D-Nal1-D -D-Phe-Ser-Mop-D Aph(Lauryl ) A 9 - L-eu -rg P-ro D-A- 0

la1-Cpa la1-Cpa

N-H N-H

(193)NH CO D NarD Cpa D Phe Ser Mop D Aph(Palmityl)6 (193)NH CO D NarD Cpa D Phe Ser Mop D Aph(Palmityl)6

Leu A 8 Leu A 8

rg Pro D Ala10 Rg Pro D Ala10

NH NH

(194)NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Butyry -- -- -- - - -- 1)-Le-u-Ar-g-Pr-o-D--Al-a10-NH-(194) NH CO-D-Nar-D-Cpa-D-Phe-Ser'-Mop-D-Aph(Butyry -- -- -- -- -- -- 1)-Le-u-Ar-g-Pr-oD--Al-a10-NH-

(195)NH CO-D-Nal1(195) NH CO-D-Nal1

9-D-Cpa-D-Phe-Ser-Mop-D-Aph(Nicoti noyl)-Leu-Arg-Pro-D-Ala10 9-D-Cpa-D-Phe-Ser-Mop-D-Aph(Nicoti noyl)-Leu-Arg-Pro-D-Ala10

-NH -NH

(196)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Pe-larg -onyl)-Leu-Arg--Pro D-A 0 (196) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Pe-larg-onyl)-Leu-Arg--Pro D-A 0

la1 NH La1 NH

(197)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-E-t)6 Le-u Ar-g Pr-o D-Al-a1 NH- (197) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-E-t)6 Le-u Ar-g Pr-o D-Al-a1 NH-

(198)NH CO D Nal' D Cpa D Phe Ser Mop D Uph(Di n P r) Leu A 9(198) NH CO D Nal' D Cpa D Phe Ser Mop D Uph (Di n P r) Leu A 9

rg Pro D A 0 Rg Pro D A 0

la1 NH La1 NH

(199)NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(Piperi dyl-C-O)-L-eu-A-rg-P-ro-D--A-la10-N-H (199) NH CO--D--Nar--D--Cpa--D--Phe--Ser--Mop--D--Aph(Piperi dyl-CO)-L-eu-A-rg- P-ro-D--A-la10-NH

(200)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Mo-rp o 1in-y1 CO-) L-eu A-rg- 9 -h (200) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(Mo-rp o 1in-y1 CO-) L-eu A-rg- 9 -h

Pro-D Ala10 Pro-D Ala10

NH NH

(201)NH CO-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-i P -r) - - --9 (201) NH CO-D-Nal!-D-Cpa-D-Phe-Ser-Mop-D-Uph(Di-i P -r) - - --9

Leu Arg Pro D Al-a10 Leu Arg Pro D Al-a10

NH NH

(202)NH CO D N-ar-D C-pa-D P-he-Ser-Mop-D U-ph-(Di Et) -Leu-Arg-Pro-D-AlaI0-NH (202) NH CO D N-ar-D C-pa-D P-he-Ser-Mop-D U-ph-(Di Et) -Leu-Arg-Pro-D-AlaI0-NH

(203)Enanthyl D NarD Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala10 (203)Enanthyl D NarD Cpa D Phe Ser Mop D Aph(Ac) Leu Arg Pro D Ala10

NH NH

(204)Lauryl-D--N-al'-D--C-pa-D--P-he-S-er-M-op-D--A-ph(Ac)- L-eu-A-rg-P- 9 (204) Lauryl-D--N-al'-D--C-pa-D--P-he-S-er-M-op-D--A-ph(Ac)- L-eu-A -rg-P- 9

ro-D--A-la-N-H ro-D--A-la-N-H

(205)Palmity-l-D Na (205) Palmity-l-D Na

0r--D Cpa--D Phe-Ser-Mop--D Aph(Ac)-Leu-Arg-Pro-D-Ala1-NH 0r--D Cpa--D Phe-Ser-Mop--D Aph(Ac)-Leu-Arg-Pro-D-Ala1-NH

(206)Butyryl D Na (206)Butyryl D Na

9 rD Cpa D Phe Ser Mop D Aph(Ac)6 Leu Arg Pro D Ala10 9 rD Cpa D Phe Ser Mop D Aph(Ac)6 Leu Arg Pro D Ala10

NH NH

(207)Nicotinoyl-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph(A -- -- -- - - -- c)--Leu--Arg--Pro--D--Ala1--NH (207) Nicotinoyl-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Aph (A -- -- -- - -- -- c)--Leu--Arg--Pro--D--Ala1--NH

(208)Pe-lar-gony-l-D Nal-1 (208) Pe-lar-gony-l-D Nal-1

6 -D Cpa--D Phe-Ser-Mop--D Aph(A c)-Leu-Arg-Pro--D Ala-10 6 -D Cpa--D Phe-Ser-Mop--D Aph(A c)-Leu-Arg-Pro--D Ala-10

NH NH

(209)Di-E-t N-CO D-N-al1 D-C-pa D-P-he S-er M-op D-A-ph(Ac)6 (209)Di-E-t N-CO D-N-al1 D-C-pa D-P-he S-er M-op D-A-ph(Ac)6

L-eu A-rg P-ro D-A-la10 N-H L-eu A-rg P-ro D-A-la10 N-H

(210)Di n Pr N-CO-D-Nar-D-Cpa -D-Phe -Ser M-op -D-Aph( Ac) -Leu -Arg - 9 (210) Di n Pr N-CO-D-Nar-D-Cpa -D-Phe -Ser M-op -D-Aph( Ac) -Leu -Arg - 9

Pro -D-Ala10 Pro-D-Ala10

-NH -NH

(211)Piperidyl CO D Na (211) Piperidyl CO D Na

6 rD Cpa D Phe Ser Mop D Aph (Ac) Leu Arg Pro D Ala1 NH 6 rD Cpa D Phe Ser Mop D Aph (Ac) Leu Arg Pro D Ala1 NH

(212)Mo-rp-hol-inyl--C-O-D-N-ar--D-C-pa--D-P-he-S-er'-M-op--D-A ph(A-c)-L-eu-A-rg-P-ro-9-D-A-la1-NH (212) Mo-rp-hol-inyl--CODN-ar--DC-pa--DP-he-S-er'-M-op--DA ph(Ac)-L-eu-A-rg- P-ro-9-DA-la1-NH

(213)Di-i-Pr N-CO-D Na-l'-D Cp-a-D Ph-e Se-r' Mo-p-D Aph( Ac-) Le-u Ar-g Pr-o-D Al-a10 (213) Di-i-Pr N-CO-D Na-l'-D Cp-a-D Ph-e Se-r' Mo-p-D Aph( Ac-) Le-u Ar-g Pr-o-D Al-a10

NH NH

(214)Di Et N-CO-D N-ar-D C-pa-D P-he S-er M-op- D Aph(A-c) -Leu -Arg-Pr-o D-Ala10 (214) Di Et N-CO-D N-ar-D C-pa-D P-he S-er M-op- D Aph(A-c) -Leu -Arg-Pr-o D-Ala10

NH NH

(215)Ben-zo-y1 D-Na-1' D-Cp-a' D-Phe'-Ser-Mo-p D Aph(-Ac) -L eu -Arg -Pr-9 (215) Ben-zo-y1 D-Na-1' D-Cp-a' D-Phe'-Ser-Mo-p D Aph(-Ac) -L eu -Arg -Pr-9

o D A-la1 NH o D A-la1 NH

(216)CHF D Nal' D Cpa'D Phe'Ser'Mop (216)CHF D Nal' D Cpa'D Phe'Ser'Mop

9 'D Aph(Ac)6 9 'D Aph(Ac)6

Leu Arg Pro D Ala1 NH Leu Arg Pro D Ala1 NH

(217)MOBA-D-Na1-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph(Ac)--Leu- -Arg--Pro-9 -- --D-Ala-10-NH (217)MOBA-D-Na1-'--D-Cpa-'--D-Phe-'-Ser-'-Mop-'--D-Aph(Ac)--Leu--Arg--Pro- 9 -- --D-Ala-10-NH

(218)CPF D-N-a1' D-C-pa' D-P-he'S-er' M-op'D-A-ph(Ac)-L-eu Arg-Pro-D Al-a10 (218) CPF D-N-a1' D-C-pa' D-P-he'S-er' M-op'D-A-ph(Ac)-L-eu Arg-Pro-D Al-a10

N-H- - N-H- -

(219)NH CO D NarD Cpa D Phe Ser Mop D Uph(Di n Butyl) 9(219) NH CO D NarD Cpa D Phe Ser Mop D Uph (Di n Butyl) 9

Leu Arg Pro D AlaI0 Leu Arg Pro D AlaI0

NH NH

(220)NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph(Propyl) Leu g o a (220) NH CO-D-Nar-D-Cpa-D-Phe-Ser-Mop-D-Uph(Propyl) Leu goa

( 1) n Buty a pa， he e op， p h( c) Leu g o a (1) n Buty a pa, he e op, p h( c) Leu g o a

( ) uty y a pa he e op ph( u yy ) Leu g P o a ( ) uty y a pa he e op ph( u yy ) Leu g P o a

( ) c a pa he， e op ph( e a gony ) Leu g o a ( ) c a pa he, e op ph( e a gony ) Leu g o a

( ) c pa h ， e op ph( u y y ) L eu g o a 和 ( ) c pa h , e op ph( u y y ) L eu g o a and

( ) a pa he， e op ph( enty 1)6 Leu g o a ( ) a pa he, e op ph( enty 1)6 Leu g o a

自上面出的化合物( ), ( ), ( ), ( ), ( ), ( ) ( ) ( 1), ( ), ( ), ( ), ( ), ( ), ( ), ( ), ( 1) ( ) ( ), ( ), ( ), ( ), ( 1), ( ), ( ) ( ), ( ) ( ), ( ), ( ), ( ), (1 ) (1 ), (1 ) (1 ), (11 , (11 , (11 ) (1 ) (1 , (1 , (1 1 (1 ), (1 ), (1 ), (1 1), (1 ), (1 )和(1 ). Compounds from above ( ), ( ), ( ), ( ), ( ), ( ) ( ) ( 1), ( ), ( ), ( ), ( ), ( ), ( ), ( ), ( 1) ( ) ( ), ( ), ( ), ( ), ( 1), ( ), ( ) ( ), ( ) ( ), ( ), ( ), ( ), (1 ) (1 ), ( 1) (1), (11, (11, (11) (1) (1, (1, (1 1 (1), (1), (1), (1 1), (1), (1 )and 1 ).

．各要求 1的 ( ) 衍生物的方法，其中 (1) 十衍生物的各固相合成方法，方法以 B . Each of the methods of claim 1 ( ), wherein (1) each of the ten derivatives is solid phase synthesis method, the method is B

休， Boc 策略，到未方法包括以下步驟 Hugh, Boc strategy, to no method includes the following steps

將十位的保的氨基酸原料以 / 或 / Put the ten amino acid raw materials in / or /

合 B B

反完全 /二氧 Boc 1 中和下介氨基酸原料 Anti-complete/dioxo Boc 1 Intermediate and lower amino acid raw materials

上順序依次將十氨基酸都到上 The top ten amino acids are in order

將最終所得到的經 F裂解得到 The resulting F-cracking is obtained.

裂解完成，水，水，化得到。．物組合物含有至少要求 1 中任項的 (1) 十衍生物或休休或生理毒性和可休或賦形。．要求的物組合物，其中 (1)十衍生物或休休或生理毒性要求中的 ( )d 衍生物或休休或生理毒性。．要求 1 中任項的 (1)十衍生物或休休或生理毒性在各物中的用途，物用于預防或治行性激素相夫疾病 ( 性激素相夫癌症， *** 、子宮膜、乳腺 ) 或于避孕或于拮抗L 、拮抗 L 休、抑制休分泌性腺激素(例 L 和/或F )和/或抑制性腺分泌矣激素(例 ***、激素和/或 )，或于降低釋放、反。．預防或治行性激素相夫疾病 ( 性激素相夫癌症， *** 、子宮膜、乳腺 )或避孕的方法，方法包括給予患者或避孕者有效量的 (1+ 衍生物或休休或生理毒性。．拮抗、拮抗L 休、抑制休分泌性腺激素(例和/或 F )和/或抑制性腺分泌矣激素(例 ***、激素和/或 )的方法，方法包括給予需要者有效量的 (1) 十衍生物或休休或生理毒性。 1 ．降低、反的方法方法包括給予需要者有效量的 (1)十衍生物或休休或生理毒性。 The cracking is completed, water, water, and chemical. . The composition contains at least one of the derivatives (1) of claim 1 or resting or physiologically toxic and reclusive or shaped. . The claimed composition, wherein (1) a ten derivative or a (d) derivative in resting or physiological toxicity requirements or rest or physiological toxicity. . The use of (1) ten derivatives or rest or physiological toxicity in claim 1 for the prevention or treatment of sex hormones (sex hormones, prostate, uterine membrane, mammary gland) or In contraception or in antagonizing L, antagonizing L, taking off hormones (such as L and / or F) and / or inhibiting gonadotropin secretion (such as estrogen, hormones and / or), or in reducing release, anti-. . A method of preventing or treating a sexual hormone-related disease (sex hormone, cancer, prostate, uterine membrane, breast) or contraception, the method comprising administering to the patient or the contraceptive an effective amount (1+ derivative or resting or physiological toxicity). . A method of antagonizing, antagonizing, or inhibiting gonadotropin (such as and/or F) and/or inhibiting gonadotropin secretion (such as estrogen, hormone, and/or), the method comprising administering an effective amount to a person in need thereof (1) Ten derivatives or rest or physiological toxicity. 1 . A reduced, reverse method comprises administering an effective amount of (1) a ten derivative or resting or physiological toxicity to a subject in need thereof.